Pigment deposits in the retrolental space of Berger: a rare feature of pigment dispersion syndrome? / Depósitos de pigmento no espaço de Berger: uma característica rara de síndrome de dispersão pigmentar?

ABSTRACT Pigment dispersion syndrome is associated with clinical features such as Krukenberg's spindles, trabecular pigmentation, Scheie's stripe and Zentmayer's ring. Another less common feature of this syndrome is retrolental pigment deposits due to anterior hyaloid detachment or a defect in the Wieger's ligament. We present two cases of pigment deposits on the posterior lens capsule. In both cases, there is bilateral dispersion of pigment throughout the anterior segment. The retrolental deposits are unilateral in the first case and bilateral in the second. Both patients report a history of ocular trauma. This is a possible important clinical sign of pigment dispersion syndrome, rarely described.

RESUMO A síndrome de dispersão pigmentar associa-se a sinais clínicos característicos como fuso de Krukenberg, hiperpigmentação da malha trabecular, linha de Scheie e anel de Zentmeyer. Um sinal menos comum dessa síndrome é o depósito de pigmento posterior ao cristalino, que ocorre por um descolamento da hialoide anterior ou um defeito no ligamento de Wieger. Apresentamos dois casos de depósitos de pigmento posterior à cápsula posterior do cristalino. Em ambos os casos, existia dispersão bilateral de pigmento por todo o segmento anterior. No primeiro caso, os depósitos eram unilaterais e, no segundo, estavam presentes em ambos os olhos. Este pode corresponder a um sinal potencialmente importante da síndrome de dispersão pigmentar, raramente descrito.

Ultrasonographic features of adenoma of the nonpigmented ciliary epithelium / 中华眼底病杂志

Objective:To analyze the ultrasonographic features of adenoma of the nonpigmented ciliary epithelium (ANPCE).Methods:A retrospective series of case studies. From January 2014 to October 2021, 31 patients (31 eyes) with ANPCE (ANPCE group) were diagnosed in the eye center of Beijing Tongren Eye Center of Beijing Tongren Hospital, Capital Medical University, and 17 patients (17 eyes) with ciliary body melanoma (control group) diagnosed at the same time were selected as the control group. There was no significant difference in age ( t=-0.564) and sex composition ratio ( χ 2=0.182) between the two groups ( P=0.576, 0.670). All patients underwent ultrasound biomicroscopy to obtain the measurement parameters: tumor height, maximum basal diameter, maximum diameter, ratio of maximum diameter to basal diameter and ratio of maximum diameter to height; tumor location, shape, internal echogenicity intensity, echogenicity uniformity, degree of sound attenuation, invasion of iris, anterior displacement of the iris, lens subluxation were observed. The measurement parameters and observation indexes of the two groups were compared by independent sample t-test and χ 2 test. Receiver operating characteristic (ROC) curve was drawn, area under the ROC curve (AUC) was determined, and parameter indicators with differential diagnosis value were screened. Results:The maximum diameter, height, maximum basal diameter, ratio of the maximum diameter to the maximum basal diameter, and the ratio of the maximum diameter to the height of the tumors in the ANPCE group and the control group were 5.64±0.98 mm, 4.24±0.59 mm, 3.66±0.71 mm, 1.58±0.34, 1.34±0.19 and 7.82±2.03 mm, 4.47±2.44 mm, 7.02±1.96 mm, 1.13±0.16, 2.09±1.06. The maximum diameter, the maximum basal diameter, and the ratio of the maximum diameter to the height of the tumor in the ANPCE group were all smaller than those of the control group, and the ratio of the maximum diameter to the maximum basal diameter was greater than that of the control group, and the differences were statistically significant ( t=-4.159,-6.808, -2.924, 6.257; P<0.05). The tumors in the ANPCE group were mainly spherical (87.1%, 27/31), with no significant acoustic attenuation (77.4%, 24/31), less invading the root iris (77.4%, 24/31), and the tumors were mostly located in the ciliary body coronal (74.2%, 23/31); tumors in the control group were mainly hemispherical (47.1%, 8/17) or spherical (47.1%, 8/17), with significant sound attenuation (76.5%, 13/17), most of the tumors invaded the iris (70.6%, 12/17), and the tumors were mostly located from the pars plana to the coronal (76.5%, 13/17). There were statistically significant differences in the position, shape, sound attenuation degree, and whether it invaded the iris between the two groups of eyes ( χ 2=15.132, 19.767, 13.118, 10.581; P<0.05). The results of ROC curve analysis showed that the ratio of the largest diameter to the largest base diameter, the degree of sound attenuation and the AUC of whether the iris was violated were higher, which were 0.881, 0.769, and 0.740, respectively. Conclusions:Ultrasound biomicroscopy is helpful in the diagnosis and differential diagnosis of ANPCE and ciliary body melanoma. The ratio of maximum diameter to maximum basal diameter, the degree of sound attenuation and whether it invades the root iris are important parameters to distinguish the two tumors.

Intravitreal and posterior subtenon triamcinolone acetonide for severe acute posterior multifocal placoid pigment epitheliopathy / Triancinolona intravítrea e sub-tenoniana para epiteliopatia pigmentar placóide multifocal posterior aguda grave

ABSTRACT A 21-year-old man presented with visual acuity of 20/200 in both eyes. The fundus picture, fluorescein angiography, and optical coherence tomography revealed severe bilateral acute posterior multifocal placoid pigment epitheliopathy and serous macular detachments. We treated the patient with triamcinolone acetonide, an intravitreal injection (4 mg/0.1 mL) in one eye and a posterior subtenon injection (40 mg/1 mL) in the other eye. Within 2 weeks the visual acuity was 20/80 in both eyes. At the 8-week follow-up visit his vision was 20/63 bilaterally. One year later the vision remained 20/63 in both eyes. In this patient, the triamcinolone acetonide injections, whether administered intravitreally or via the posterior subtenon route, achieved similar anatomic and functional recovery results.

RESUMO Um homem de 21 anos apresentou acuidade visual de 20/200 em ambos os olhos. O quadro de fundo de olho, angiofluoresceinografia e a tomografia de coerência óptica revelaram epiteliopatia pigmentar placóide multifocal posterior aguda e descolamento macular seroso. Tratamos o paciente com triancinolona acetonida, uma injeção intravítrea (4 mg/0,1 ml) em um olho e uma injeção subtenoniana posterior (40 mg/1 ml) no outro olho. Após 2 semanas, a acuidade visual foi de 20/80 em ambos os olhos. Na visita de acompanhamento de 8 semanas, sua visão foi de 20/63 bilateralmente. Um ano depois, a visão permaneceu 20/63 em ambos os olhos. Neste paciente, as injeções de triancinolona, administradas por via intravítrea ou por via subtenoniana posterior, obtiveram resultados semelhantes na recuperação anatômica e funcional.

Secondary glaucoma induced by bilateral acute depigmentation of the iris / Glaucoma secundário à despigmentação bilateral aguda da íris

Abstract We report a case of a middle-aged woman who developed acute, bilateral, symmetrical, slightly transilluminating depigmentation of the iris and pigment discharge into the anterior chamber following the use of oral moxifloxacin for bacterial sinusitis. She had been misdiagnosed as having autoimmune uveitis, treated with steroids and tropicamide, and underwent severe ocular hypertension and glaucoma despite posterior correct diagnosis.

Resumo Relato de um caso de uma paciente do sexo feminino de meia idade que desenvolveu despigmentação bilateral simultânea aguda com dispersão de pigmentos na câmara anterior e discreta transiluminação após o uso de moxifloxacino oral para tratamento de sinusite bacteriana. Ela Havia sido diagnosticada com uveite autoimune e tratada com corticosteroide tópico e tropicamida e evoluiu com hipertensão ocular grave e glaucoma apesar de ,posteriormente, o diagnóstico ter sido correto.

Frequency of fibromyalgia syndrome in patients with central serous chorioretinopathy / Frequência de síndrome de fibromialgia em pacientes com coriorretinopatia serosa central

ABSTRACT Purpose: To ınvestigate frequency of fibromyalgia syndrome (FMS) among patients with central serous chorioretinopathy (CSCR). Methods: The study included 83 patients with CSCR and 201 age- and sex-matched healthy controls; the mean age was 47.5 ± 11.3 years in the CSCR group (18 women; 21.7%) and 47.2 ± 11.2 years in the control group (44 women; 21.9%). All participants were assessed for FMS based on 2010 American College of Rheumatology diagnostic criteria and for depression and anxiety with the Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI). Results: FMS was diagnosed in 35 patients (42.2%) from the CSCR group and in 21 individuals (10.4%) from the control group (p<0.001). It was found in 77.77% of the women (14/18) and 32.3% of the men (21/65) in the CSCR group and in 22.7% of the women (10/44) and 7.0% of the men (11/157) in the control group. Familial stress, BDI and BAI scores were higher in the patients with FMS than in those without. When independent risk factors were evaluated by logistic regression analysis, it was found that only the presence of familial stress was a significant risk factor for FMS. Conclusions: Patients with CSCR should be assessed for the presence of FMS, and this should be taken into consideration when developing a treatment plan. Further studies with a larger sample size are needed to clarify the relationship between FMS and CSCR.

RESUMO Objetivo: Investigar a frequência da fibromialgia (FMS) entre os pacientes com coriorretinopatia serosa central (CSCR). Métodos: O estudo incluiu 83 pacientes com CSCR e 201 controles saudáveis pareados por idade e sexo. Todos os participantes foram avaliados com base nos critérios de diagnóstico de FMS do American College of Rheumatology de 2010 (ACR), Beck Anxiety Inventory (BAI) e Beck Depression Inventory (BDI). Resultados: A idade média foi 47,53 ± 11,33 anos no grupo CSCR (18 mulheres; 21,7%) e 47,19 ± 11,19 anos (44 mulheres; 21,9%) no grupo controle. FMS foi diagnosticada em 35 pacientes (42,2%) do grupo CSCR e em 21 indivíduos (10,4%) do grupo controle (p<0,001). FMS foi encontrado em 77,77% das mulheres (14/18) e 32,3% dos homens (21/65) no grupo CSCR e em 22,7% das mulheres controles (10/44) e 7,0% dos homens controles (11/157). Estresse familiar, BDI e BAI foram maiores nos pacientes com FMS em comparação com aqueles sem FMS. Quando os fatores de risco independentes foram avaliados por análise de regressão logística, verificou-se que apenas a presença de estresse familiar foi um fator de risco significativo para FMS. Conclusões: Os pacientes com CSCR devem ser avaliados para presença de FMS e a FMS deve ser levada em consideração durante o desenvolvimento de um plano de tratamento. São necessários mais estudos com maior tamanho da amostra para esclarecer relações entre FMS e CSCR.

Mediated effects of endoplasmic reticulum stress on light-induced apoptosis and inflammation of human retinal pigment epithelial cell / 中华实验眼科杂志

Background The light damage model of retinal pigment epithelium (RPE) cells is a research direction of retinal degeneration diseases,and RPE cell apoptosis induced by light damage and inflammation is an important pathologic basis of light-induced RPE cell damage.However,whether endoplasmic reticulum stress (ERS) paticipates in light-induced RPE cell damage is rarely reported.Objective This study was to explore the effects of ERS on light-induced RPE cell damage.Methods Human RPE cell line (ARPE-19) was cuhured,and light damage models were created by irradiating the cells for 3-,6-,12-and 24-hours with white fluorescent lamp with the intensity of (2 000±500)lx for the selection of optimal irradiating time,and the cells in the normal control group were cultured in the dark environment.The cells were divided into normal control group,light exposure group and 4-phenylb utyric acid (4-PBA) pretreated +light exposure group.The cells from 4-PBA pretreated +light exposure group were cultued firstly with 4-PBA for 30 minutes and followed by light exposure for 12 hours.The apoptisis rate of the cells and intracellular reactive oxygen species (ROS) content were detected by flow cytometry;the concentrations of interleukin 1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the cell supernatant were assyed by ELISA.The relative expressing levels of activating transcription factor 6 (ATF-6),C/enhancer binding protein homologous protein (CHOP) and caspase-12 mRNA and protein in the cells were detected by real-time quantitative PCR and Western blot,respectively.Results The cultured cells showed a long spindle shape,the border was not clear,the cytoplasm was degranulation,and the cell fragments increased.Flow cytometry showed that compared with the normal control group,the ROS content in the cells and the apoptosis rate were evidently increased with the lapse of light exposure time (F=763.00,119.30,both at P＜0.01).ELISA results showed that the concentrations of IL-1β and TNF-α in the cell supernatant were significantly higher in the light exposure 6-hour group than those in the normal control group with the peak value in the light exposure 12-hour group.Compared with the normal control group,the relative expression levels of ATF-6,CHOP and caspase-12 mRNA and protein in the cells were elevated in the light exposure group and peaked in the light exposure 12-hour group.In addition,the relative expression levels of ATF-6 mRNA,CHOP mRNA and caspase-12 mRNA in the cells were significantly reduced in 4-PBA pretreated+light exposure group compared with the light exposure group (F=281.69,473.88,308.45,all at P＜0.01),and their proteins were also significantly reduced (F =47.86,57.93,106.59,all at P ＜ 0.01).The apoptosis rate,concentrations of IL-1β and TNF-α in the cell supernatant were significantly reduced in 4-PBA pretreated+light exposure group compared with the light exposure group (F =88.64,245.47,101.01,all at P＜0.01).Conclusions The light exposure at (2 000 ± 500)lx induces intracellular ROS accumulation and activates the ERS response,which results in apoptosis and inflammatory process of human RPE cells.4-PBA,a inhibitor of ERS,can suppress light-induced ERS response and therefore reduces the apoptosis rate and inhibits inflammatory process.

Comparison of retinal histomorphology following laser photocoagulation using 577 nm subliminal micropulse laser versus 577 nm laser in pigmented rabbits / 中华实验眼科杂志

Background Studies showed that 577 nm subliminal micropulse photocoagulation for retinal diseases is more effective and much safer than 577 nm laser,but its mechanism and sensitive target cells are still unelucidated.Objective This study was to compare the histomorphology changes of rabbit retinas following 577 nm subliminal micropulse excitation and 577 nm laser for retinal photocoagulation and offer a conference for the clinical application of 577 nm subliminal micropulse excitation.Methods Twenty-six Chinese pigment rabbits were randomly divided into normal control group (2 rabbits),577 nm laser photocoagulation group (6 rabbits) and subliminal micropulse photocoagulation group (18 rabbits),in which the rabbits from subliminal micropulse photocoagulation group were subgrouped into 9％,12％ and 15％ subthreshold photocoagulation groups according to the different workload rates,and retinal photocoagulation was performed based on grouping.No treatment was carried out in the normal control group.Fundus camera and OCT were obtained after photocoagulation,and the rabbits were sacrificed to prepare the specimen of eyeball wall.Hematoxylin and eosin staining was employed to examine the histopathological change of choroid and retina under the light microscope.Results The retinal morphology was normal on the fundus color photography and OCT in the normal control group.Obscure of retinal structure and slight edema of retinal neuroepithelial layer with obscure of retinal pigment epithelium (RPE) was found respectively in the 9％ and 12％ subthreshold photocoagulation group,and serious edema of retinal neuroepithelial layer with local RPE elevation was visible in the 15％ subthreshold photocoagulation group.The laser spot was invisible in various subliminal micro pulse groups.However,retinal photocoagulation spots,multifocal elevation of retinal layer and serious detachment of retinal neuroepithelium were found in the 577 nm laser group.Retinal histopathological examination revealed that the photoreceptors,bipolar cells and retinal ganglion cell (RGC) layers were normal,while choroidal vessel deformation and bleeding were visible in the 9％ and 12％ subthreshold photocoagulation groups,and only photoreceptor membrane swelling was seen in the 15％ subthreshold photocoagulation group.However,retinal structure abnormality was displayed in 577 nm laser group,including the structural disorders of inner and outer nuclear layers and RGC layer as well as thinning of RPE layer.Conclusions 577 nm nicropulse laser under threshold is sensitive for RPE and choroid rather than retina neurepithelium,which can play a treating role and also does not damage retina seriously.However,577 nm laser photocoagulation results in retinal structure damage.

Dynamic changes of FasL protein expression in retinal tissue with aging in retinal degeneration mice / 中华实验眼科杂志

Background Retinal transplantation is a new approach to the treatment of retinal degeneration diseases,and how to avoid or reduce the immune rejection after transplantation is a problem.In experimental studies on retinal transplantation,C57BL/6 mice are often used as donors and rd mice serve as recipients.Studies showed that Fas ligand (FasL) protein induces the apoptosis of Fas+ inflammatory cells by FasL/Fas signal pathway,speculating that FasL protein is associated with immune rejection after transplantation.Objective The aim of this study was to investigate FasL protein expression change in retinas of C57BL/6 mice and rd mice with aging and reveal the immune characteristics of the mouse retinas.Methods The frozen sections of eyeball from C57BL/6 mice and rd mice at the age of postnatal (PN)-0 week,PN-1 week,PN-2 week,PN-3 week and PN-4 week were prepared.The expression of FasL protein in the mouse retinas was examined by immnofluorescense technique.Images were acquired by fluorescence microscope and analyzed semi-quantitively by software from laser scanning confocal microscope as the fluorescence intensity (FI).The results were compared among different strains of mice.Results The retina developed imperfectly in PN-1 week C57BL/6 mice and FasL protein was positively expressed in the whole retina.In PN-2,3 and 4 week C57BL/6 mice,retinas finished the development with 10 layers,and retinal pigment epithelium (RPE),inner segment (IS),outer limiting membrane (OLM),outer plexiform layer (OPL),inner nuclear layer (INL),inner plexiform layer (IPL) and ganglion cell layer (GCL).Retinal structure and expression of FasL protein in the whole retina of rd mice in the PN-1 week were similar with C57BL/6 mice,however,ONL cells of rd mice were evidently decreased with aging.The RPE,OPL,INL,IPL and GCL expressed the FasL protein in PN-2,PN-3 and PN-4 week rd mice.The mean FI of FasL protein in the RPE layer was 184.199±16.747,186.797±7.904 and 184.319± 18.795 in rd mice of PN-2 week,PN-3 week and PN-4 week,which were significantly higher than 160.402±22.851,160.995 ±22.799 and 105.787 ± 17.676 in C57BL/6 mice (t =-3.360,P =0.002;t'=-4.277,P =0.000;t =-12.175,P=0.000).There were not significant differences in the mean FI of FasL protein in IPL between C57BL/6 mice and rd mice at ages of PN-2 week,PN-3 week and PN-4 week (all at P＞0.05).Conclusions The cells of retinal ONL are gradually decreased with the development of rd mice,and FasL protein expression intensity in RPE is evidently enhanced in rd mice compared with C57BL/6 mice.

Influence of repetitive intravitreal ranibizumab for neovascular age-related macular degeneration on retinal pigment epithelium and choroidal thickness / 中华实验眼科杂志

Background Intravitreal injection of ranibizumab (IVR) is one of the most effective therapies for neovascular age-related macular degeneration (nAMD).Understanding the influence of IVR on retinal pigment epithelium (RPE) and choroidal thickness is helpful for us to choose the operative times and timing based on pharmacologic effects and tissue response.However,limited studies are available about quantitative analysis of RPE atrophic area and subfoveal choroidal thickness after IVR for nAMD.Objective This study was to report the changes of RPE atrophic area and subfoveal choroidal thickness after IVR for nAMD.Methods A prospective series cases-observational study was designed.Forty-one eyes of 41 consecutive patients with nAMD were enrolled in Renmin Hospital of Wuhan University from January 2015 to June 2015,and written informed consent was obtained from each patient prior to entering the cohort.The affected eyes received intravitreal injection of 0.05 ml ranibizumab (10 mg/ml) and then followed up monthly for 12 months.The RPE atrophy area around macula and subfoveal choroidal thickness were measured by a newly developed RPE analysis software spectral-domain optical coherence tomography (OCT) and enhanced depth imaging of SD-OCT (EDI-OCT),respectively,and the RPE atrophy area and choroidal thickness changes were compared before IVR and 3,6 and 12 months after IVR.The correlation between RPE atrophy area and choroidal thickness before and after IVR was analyzed.Results All the patients finished the treating procedure and follow up.The visual acuity (logMAR) after IVR was considerably improved in comparison with before IVR (F=7.631,P＜0.001).The mean subfoveal choroidal thickness value was (264.55 ± 100.95) μm before IVR,and that of 3,6,12 months after IVR was (247.42±105.46),(246.81± 99.85) and (253.97±101.15)μm,respectively,showing a significant difference among different time points (F =2.030,P ＜ 0.05),and the mean subfoveal choroidal thickness values 3,6,12 months after IVR were evidently thinned in comparison with before IVR (all at P＜0.05).No significant difference was found in RPE atrophic area among different time points (F=0.116,P =0.951).Weak linear correlations were seen between RPE atrophy area and choroidal thickness (r =-0.185),the RPE atrophy area change values and choroidal thickness change values between IVR ＞ 6 times and ≤ 6 times (r =0.297,-0.327),but these results were not statistically significant (P =0.248,0.282,0.103).At the end of the follow up,weak linear correlations were seen in RPE atrophy area change values and choroidal thickness change values with IVR times (r,=-0.266,0.342),but these results were not statistically significant (P =0.148,0.060).Conclusions IVR for nAMD can lead to subfoveal choroid atrophy instead of RPE atrophy.IVR does not accelerate the atrophy progression of both RPE and choroid.

Bilateral acute depigmentation of the iris: a case report / Despigmentação aguda bilateral da íris: um relato de caso

ABSTRACT Bilateral acute depigmentation of the iris (BADI) is a new clinical entity of unknown etiology and is characterized by bilateral, symmetrical, and simultaneous depigmentation of the iris with focal or diffuse stromal atrophy; this condition generally has a good prognosis. We present a case of a 26-year-old woman who noted a spontaneous change in the iris color in both eyes in the last 2 months. The ophthalmological findings were atrophy of the iris stroma and pigmentation of the trabecular meshwork, without affecting the pigmented epithelium of the iris. Her intraocular pressure was normal and the visual acuity was 20/20 in both eyes.

RESUMO A despigmentação aguda bilateral da íris (DABI) é uma nova entidade clínica caracterizada pela despigmentação bilateral, simétrica e simultânea da íris, com atrofia focal ou difusa do seu estroma, geralmente com bom prognóstico. Apresentamos o caso de uma mulher de 26 anos de idade que procurou atendimento médico em nosso serviço com queixa de mudança espontânea na cor da íris de ambos os olhos nos últimos dois meses. Os achados oftalmológicos observados durante o exame clínico foram atrofia do estroma da íris e pigmentação da malha trabecular, sem afetar o epitélio pigmentado da íris. A pressão intraocular era normal e acuidade visual de 20/20 em ambos os olhos.

Induction of docosahexaenoic acid to expression of heme oxygenase-1 in retinal pigment epithelial cells / 中华实验眼科杂志

Background Oxydative stress is an important pathogenesis of age-related macular degeneration.Resent evidences indicate that docosahexaenoic acid (DHA) plays an important role during the development of retinal photoreceptor cells and protect the cells against oxydative stress by inducing the expression of heme oxygenase-1 (HO-1).However,whether DHA can induce the expression of HO-1 in human retinal pigment epithelium (RPE) cells is unelucidated.Objective This study was to investigate the effect of DHA on the expression of HO-1 in RPE cells and its molecular mechanism.Methods Human RPE cell line ARPE-19 was cultured in vitro and treated with 30,50,100 and 120 μmol/L DHA for 4 to 24 hours,respectively,and the cells were cultured without DHA as the control group.The cytotoxicity of DHA was detected by lactate dehydrogenase(LDH),and the expression of HO-1 mRNA and protein were detected by real-time PCR and Western blot assay,respectively.The enzymatic activity of HO-1 was detected by colorimetry.The reactive oxygen species (ROS) proportion in the cells was detected using fluorescence probe H2 DCFDA,and immunofluorescence technology was adopted to detect the nuclear translocation of nuclear facotor-E2-related factor 2 (Nrf2).The expression of Nrt2 protein in the cells was detected by Western blot after intervention of ROS inhibitor N-acetylcysteine (NAC) and transfection of Nrf2 small interfering RNA (siRNA).Results The LDH leakage rate was significantly different after 0,3,50,100 and 120 μmol/L DHA treated the cells for 24 hours (F=8.14,P＜0.05),and the LDH leakage rate in the 120 μmol/L DHA group was significantly higher than that of 0,30,50 and 100 μmol/L DHA group (all at P＜0.05).The relative expression levels of HO-1 mRNA and HO-1 protein or HO-1 enzymatic activity in the cells were significantly different among different concentrations of DHA group in 8 hours after treatment (F=16.24,P＜0.05;F=11.34,P＜0.05;F=11.81,P＜0.05),and the expressions of these factors were considerably higher in the 30,50 and 100 μ mol/L DHA group than those in the 0 μmol/L DHA group (all at P＜0.05).The ROS relative fluorescence intensity and nuclear Nrf2 positive cells proportion were statistically significant among different concentrations of DHA groups (F =11.08,P ＜ 0.05;F=16.42,P＜0.05),and the ROS relative fluorescence intensity and nuclear Nrf2 positive cells proportion were evidently higher in the 30,50 and 100 μmol/L DHA group than those in the 0 μmol/L DHA group (all at P＜0.05).The relative expression levels of HO-1 protein and the proportion of nuclear Nrf2 positive cells were significantly lower in the NAC pretreated 100 μmol/L DHA group than those in the 100 μmol/L DHA group.In addition,the HO-1 relative expression level and the positive cells proportion of nuclear Nrf2 were significantly lower in the of Nrf2 siRNA transfection group than those in the blank siRNA transfection group (both at P＜0.05).Conclusions DHA with concentration below 100 μ mol/L can protect RPE cells from oxidative stress by inducting the expression of HO-1 in the cells via ROS/Nrf2 pathway.

Promoting effect of p75NTR receptor overexpression on oxidative stress injury in human retinal pigment epithelium cells / 中华实验眼科杂志

Background Choroidal neovascularization (CNV) is the primary pathogenic cause of many fundus diseases.Oxidative stress injury of retinal pigment epithelial (RPE) cells plays important role in angiogenesis of choroid new blood vessels.Oxidative stress injury can active p75NTR receptor, a member of tumor necrosis factors family,resulting in the proliferation of vascular endothelial cells.However, the mechanisms of vascular endothelial cell proliferation remain unclear.Objective This study was conducted to investigate the effect of p75NTR overexpression on CNV and the relative mechanism.Methods The ARPE-19 cell line was used in this study.RPE cells were transfected with p75NTR receptor overexpressed plasmid, and untransfected cells served as the control group.The transfected results were verified by reverse transcription-PCR and Western blot assay.Viability of the cells over time was determined in the p75NTR receptor plasmid transfected group by using BrdU assay.The percentage of apoptotic cells was detected by flow cytometry using Annexin V-FITC/PI fluorescence staining.The percentage of reactive oxygen species (ROS) expression in the cells was detected by using H2 DCFDA fluorescence and flow cytometry.Mitochondrial membrane potential and cytochrome C expression were examined under the confocal microscope.The protein expressions of cleaved caspase-3, Fas and VEGF were determined by Western blot assay.Results The relative expression level of p75 NTR receptor mRNA was (6.11 ±0.77) times higher than that of the control group, and relative expression level of p75NTR receptor protein in the cells in the p75NTR receptor plasmid transfected group was (7.42±0.48) times higher than that in the control group (t=11.49 and 23.17 ,both at P＜0.01).The absorbency values of the p75NTR receptor plasmid transfected group were (93.12±0.56) ％ , (86.30±0.66) ％ , (72.53-±0.86) ％ and (60.77 ±2.81) ％ in 12,24,36 and 48 hours after plasmid transfection, which were significantly lower than 100％ in the control group, and the apoptotic percentages were evidently higher than that in the control group (all at P＜0.05).The relative fluorescence intensity of ROS fluorescence in the p75NTR receptor plasmid transfected group was 2.4 times higher than that in the control group,showing significant difference (t=16.45, P＜0.01).The positive expressing rate of mitomarker (mitochondrial membrane potentials) was 100％ in the control group and (37.30± 2.06)％ in the p75NTR receptor plasmid transfected group, with significant difference between them (t =57.71,P＜0.01).The fluorescence intensity of cytochrome C expression was elevated in the p75NTR receptor plasmid transfected group compared with the control group.Compared with the control group,the expressing levels of cleaved caspase-3 ,Fas and VEGF165 proteins in the cells were significantly raised in the p75NTR receptor plasmid transfected group (all at P＜0.01).Conclusions Overexpression of p75NTR receptors in RPE cells leads to mitochondrial damage and cellular apoptosis and the secretion of VEGF protein, which sequentially promote CNV.P75NTR receptor may be another important regulation pathway in RPE oxygen damage.

Idiopathic polypoidal choroidal vasculopathy masquerading as choroidal tumors: one year follow-up of a peripheral lesion / Vasculopatia polipoidal idiopática da coroide simulando tumores da coroide: um ano de seguimento de uma lesão periférica

ABSTRACT This case report describes peripheral idiopathic polypoidal choroidal vasculopathy (IPCV) with a collection of small aneurysmal dilations that masqueraded as choroidal tumors in an elderly patient. A 68-year-old African American woman was referred to us with a suspected diagnosis of asymptomatic vascular choroidal tumor and choroidal capillary hemangioma, affecting the temporal peripheral fundus. Upon examination, optical coherence tomography (OCT) revealed two large hemorrhagic pigment epithelium detachments (PED), and indocyanine green angiography (ICG) confirmed the diagnosis of IPCV. One year later, there was reduction in the hemorrhagic pigment epithelium detachments and the lesion took on a different appearance, resembling a choroidal osteoma. No treatment was necessary despite the presence of multiple polyps. IPCV is a rare condition that can resemble other choroidal diseases depending on the stage of presentation. OCT is the best tool to determine the characteristics of the lesions, and indocyanine green angiography should be used to confirm the diagnosis. Not all cases require treatment.

RESUMO Relato de um caso de vasculopatia polipoidal idiopática da coroide (IPCV) com múltiplas dilatações aneurismáticas em região temporal periférica da retina, em uma paciente idosa que assemelhou-se com alguns tumores de coroide no seguimento de um ano. Paciente de 68 anos da raça negra, assintomática, foi encaminhada com a hipótese diagnóstica de um tumor vascular de coroide e hemangioma capilar da coroide, em região temporal inferior periférica da retina. Ao exame de tomografia de coerência óptica (OCT) era observado dois grande descolamentos de epitélio pigmentado (DEP), sendo confirmado o diagnóstico de vasculopatia polipoidal idiopática da coroide pela angiografia com indocianina verde (ICG). Após um ano, houve absorção do descolamento do epitélio pigmentado hemorrágico assemelhando-se assim ao osteoma de coroide. Nenhum tratamento foi necessário apesar da quantidade dos pólipos. A vasculopatia polipoidal idiopática da coroide é uma doença rara que, dependendo do estágio da apresentação, pode se assemelhar com algumas doenças da coroide. A tomografia de coerência óptica pode ilustrar melhor as características das lesões e a ICG confirma o diagnóstico. Nem todos os casos necessitam ser tratados.

Bilateral acute iris transillumination (BAIT) initially misdiagnosed as acute iridocyclitis / Transiluminação de íris aguda bilateral (BAIT) inicialmente diagnosticada como iridociclite aguda

Bilateral acute iris transillumination (BAIT) is a relatively new clinical entity characterized by bilateral acute loss of iris pigment epithelium, iris transillumination, pigment dispersion in the anterior chamber, and sphincter paralysis. We report the case of a 30-year-old male who was initially diagnosed with acute iridocyclitis in a different clinic and treated with topical and systemic corticosteroids. He was referred to our clinic to seek another opinion because his symptoms did not improve. An ocular examination revealed bilateral pigment dispersion into the anterior chamber, diffuse iris transillumination, pigment dusting on the anterior lens capsule, atonic and distorted pupils, and increased intraocular pressure, suggesting a diagnosis of BAIT rather than iridocyclitis. Clinicians should be aware of the differential diagnosis of syndromes associated with pigment dispersion from iridocyclitis to avoid aggressive anti-inflammatory therapy and detailed investigation for uveitis.

A transiluminação de íris aguda bilateral (do inglês, bilateral acute iris transillumination, BAIT) é uma entidade clínica relativamente nova, caracterizada pela perda aguda bilateral do epitélio pigmentado da íris, transiluminação iriana, dispersão de pigmentos na câmara anterior, e paralisia do esfíncter pupilar. Nós relatamos o caso de um homem de 30 anos que foi diagnosticado com iridociclite aguda e tratado com corticosteroides tópicos e sistêmicos. Ele foi encaminhado ao nosso serviço para outra opinião, porque seus sintomas não melhoram com a terapia. Um exame oftalmológico revelou dispersão bilateral de pigmentos para a câmara anterior, transiluminação difusa de íris, pigmento difusa na cápsula anterior do cristalino, pupilas atônicas e distorcidas, e um aumento da pressão intraocular, o que sugere um diagnóstico de BAIT em vez de iridociclite. Os médicos devem estar cientes do diagnóstico diferencial das síndromes associadas à dispersão de pigmento com a iridociclite para evitar a terapia antiinflamatória agressiva e investigação detalhada para uveíte.

Study on human adipose mesenchymal stem cells differentiating into retinal pigment epithelial-like cells and its in vivo application / 中华实验眼科杂志

Background Stem cell transplantation represents a promising treatment option for patients suffering from degenerative disorders.Accumulating evidences indicate that mesenchymal stem cells (MSCs) are able to differentiate into retinal pigment epithelial (RPE)-like cells.However,MSCs are difficult to obtain.Human adipose mesenchymal stem cells (ADSCs) are proved to have similar properties to MSCs,but relevant study is less.Objective This study was to assess the feasibility of human ADSCs differentiating into RPE-like cells and the safety of its application in vivo.Methods The third generation of human ADSCs were incubated into 6-well plate,and 100 ng/ml epithelial growth factor,50 μ mol/L taurine and 5×10-7 mol/L retinoic acid were added into the medium 12 hours after cultured to induce the cells,and conventional cultured cells were used as the control group.Induced cells were traced with PKH26,and Pan-cytoke ratin (Pan-CK) monoclonal antibody was used to identify the cells under the fluorescence microscope.Induced RPE-like cell suspension of 1 μl was intravetreally injected in the right eyes of 6 BALB/c mice,and equal volume of PBS was used in the same way in another 6 mice.The animals were sacrificed 1 month after injection,and the retinal morphology was examined by histopathology under the optical microscope.The ultrastructure of retinal ganglion cells (RGCs) was examined by the transmission electron microscope.The use and care of the animals complied with Regulations for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission.Results Cultured human ADSCs grew well with the slender polygone shape.Cell membranes showed the red fluorescence for PKH26 after induced.In addition,Pan-CK was expressed in the cell membranes with the red fluorescence in the induced cells,but the response was absent in the control cells.One month after intravitreal injection,induced cells located on the retinal surface,and the retinal morphology was clear under the optical microscope.No abnormality in RGCs was seen under the transmission electron microscope.Conclusions Human ADSCs can differentiate into RPE-like cells after induction.PKH26 can mark induced cells well.There is no adverse effect of induced cells on retina after intravitreal injection in a short-term duration in mice.

Improvement of RPE cells growth and metabolism abilities by mitochondrial transfer of neural stem cells / 中华实验眼科杂志

Background Researches showed that stem cells can rescue damaged cells through mitochondrial transfer.This mode has been used to regenerative cell-based therapy.Retinal pigment degeneration is an eye disease of retinal pigment epithelial (RPE) cell apoptosis as pathogenetic mechanism.Whether stem cells can repair the target cells by above mechanism has not been clarified.Objective This study was to investigate the influence of mitochondrial transfer on the function of RPE cells.Methods The RPE cells of Long-Evans rats were isolated and cultured and the third generation of cells were used in sequential experiment.The cells were identified by detecting the expressions of RPE65 and Bestrophin proteins with immunofluorescence stain.Mouse neural stem cells (NSCs) (C17.2 strain) with green fluorescence protein (GFP) and without GFP were cultured.Mitotracker-green and Mitotracker-red staining were separately used to labeled the mitochondria of RPE cells and NSCs.RPE cells were cocultured with NSCs,and wheat germ agglutinin (WGA) was used to mark the tunneling nanotubes (TNT) between the two kinds of cells,and then the mitochondrial migration in TNT was exhibited by the laser scanning confocal microscope.The proportion of RPE cells in different cycles was assayed after marked with propidium iodide (PI) by flow cytometry.The contents of ATP,ADP and AMP in RPE cells were detected by high performance liquid chromatography (HPLC).Results The third-generation of RPE cells grew well with the RPE65-and Bestrophinpositive rate ＞85％.The Mitotracker-red-labeled rates of NSCs and RPE cells were no less than 95％.TNT structure was seen to appear the blue fluorescence between RPE cells and NSCs 24 hours after co-cultured and the red dye mitochondria from NSCs migrated toward red dye mitochondria from RPEs with the lapse of time.The RPE cell proportion reduced in G1 phase and increased by 5％ and 2％ in the S phase and G2/M phase respectively after mitochondrial transfer than before (P=0.016,0.114,0.189).The contents of ATP,ADP and AMP in the RPE cells were (8.77 ±3.68),(2.76±0.92) and (1.07 ±0.65) μg/mg after cell co-culture,and those before co-culture were (11.29±2.29),(3.12±0.95) and (1.59± 1.22) μg/mg,without significant differences between them (P =0.370,0.668,0.553).Conclusions NSCs can transfer normal mitochondria to co-cultured RPEs via TNT structure.Mitochondrial exchange might be one of therapeutic mechanisms of NSCs recuing damaged RPE cells.

Changes of serum lipids in patients with Bietti crystalline dystrophy / 中华实验眼科杂志

Background Bietti crystalline dystrophy (BCD) is a congenital and autosomal recessive hereditary eye disease characterized by multiple glistening intraretinal crystals scattered over the fundus.Studies determined abnormality of fatty acid metabolism probably is associated with BCD.However,the study on the alteration of blood lipid level in BCD patients is rare.Objective This trail was to study the change of serum lipids in BCD patients.Methods A total of 50 patients with bilateral BCD and 50 matched healthy volunteers were included from November 2011 to March 2013 in Beijing Tongren Eye Center with the approval of Ethic Committee of Beijing Tongren Hospital.Written informed consent was obtained from each subject before any medial examination.Peripheral blood of 3 ml was collected from the subjects.The serum concentrations of triglyceride (TG),total cholesterol (TC),low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) were measured and analyzed.The examination outcome was identified based on the criteria of China Adult Dyslipidemia Prevention Guideline (Version 2007).Results Abnormality of serum lipid content was detected in 58.00％ patients (29/50),and hypertriglyceridemia and hypercholesteremia were in 34.48％ (10/29),respectively,and mixed hyperlipidaemia was in 27.59 ％ (8/29).The serum levels of TG,TC and LDL-C were (1.63± 1.19) mmol/L,(5.10±1.05) mmol/L and (3.27±0.97) mmol/L in the BCD group,which were significantly higher than (0.93± 0.33) mmol/L,(4.33 ±0.56) mmol/L,(2.63 ±0.51) mmol/L of the normal group (t =4.036,4.496,4.095,all at P=0.000).Conclusions The serum lipid levels elevate in BCD patients,which might be related to the occurrence of BCD.

Modulation of PDGF on the expression of MMP-2,MMP-9 and TIMP-1 in human RPE cells / 中华实验眼科杂志

Background Researches showed that platelet-derived growth factor (PDGF) modulate the expression of matrix metalloproteinase/tissue inhibitor of metalloproteinase (MMP/TIMP) in cells,but the association of expression of MMP/TIMP in retinal pigment epithelial (RPE) cells and the dose and active time of PDGF is unclear.Objective This study was to observe the effects of PDGF on the expressions of MMP-2,MMP-9 and TIMP-1 in cultured RPE cells in vitro.Methods RPE cell line,ARPE-19,was calculated in vitro,and the cells were divided into 5 groups when they reached 70％-80％ confluence.Different concentrations (0,0.1,1,10,50 mg/L) of PDGF was added into the medium respectively for 36 hours,and the expressing levels of mRNA and protein of MMP-2,MMP-9 and TIMP-1 were detected by reverse transcription PCR (RT-PCR) and Western blot assay.In addition,RPE cells in PDGF group were treated with 10 mg/L PDGF for 24,36,48 hours respectively to detect the expressions of mRNA and protein of MMP-2,MMP-9 and TIMP-1 in the cells and to compare with the control group without PDGF.Results PDGF stimulated proliferation of RPE cells in a dose-and time-dependent manner.As the increase of the PDGF concentrations,the expression values of MMP-2 mRNA and MMP-9 mRNA in RPE cells were gradually elevated,with a statistically significant difference among various groups (MMP-2 mRNA:F=79.304,P=0.000;MMP-9 mRNA:F =8.465,P=0.003),and the expressions of MMP-2 mRNA and MMP-9 mRNA were significantly higher in the 1,10,50 mg/L PDGF groups compared with 0 mg/L PDGF normal control group (all at P＜0.05).Also,the expression values of MMP-2 and MMP-9 proteins in RPE cells were gradually elevated with the increase of PDGF concentrations,showing statistically differences among the groups (MMP-2:F=26.550,P=0.000;MMP-9:F=80.993,P=0.000).Compared with the 0 mg/L PDGF group,MMP-2 and MMP-9 expression levels in the 1,10,50 mg/L PDGF groups were significantly up-regulated (all at P＜ 0.05).However,the expression levels of TIMP-1 mRNA and protein group in the cells were not significantly different among various groups (mRNA:F =0.143,P =0.962 ; protein:F =1.955,P =0.178).The expression levels of M MP-2 mRNA,M MP-9 mRNA in the cells were increased in the PDGF group compared with the control group at different time points (MMP-2 mRNA:Ftime =83.250,P=0.002 ; MMP-9 mRNA:Ftime =6.785,P =0.019).Also,the expression values of MMP-2 and MMP-9proteins in RPE cells were increased in the PDGF group compared with the control group at different time points (MMP-2:Ftime =1 l.185,P =0.041 ; MMP-9:Ftime =968.413,P =0.000).The expression levels of MMP-2 and MMP-9 mRNAs and proteins were significant between the two groups at different time points (all at Pgroup =0.000;all at Ptime＜0.05).While the expression changes of TIMP-1 werc not significant between the two groups and among various time points (all at P＞0.05) Conclusions PDGF up-regulates MMP-2 and MMP-9 expressions in RPE cells in a dose-and time-dependent manner.But,PDGF dose not alter the expression of TIMP-1.These results indicate that PDGF disrupt the balance of MMP/TIMP,which may damage the extracellular matrix and therefore facilitate the migration of RPE cells in the pathogenesis of proliferative vitreoretinopathy.

Torpedo maculopathy with an anisometropic amblyopia in a 5-year-old Caucasian girl: case report / Maculopatia torpedo numa criança caucasiana de 5 anos de idade com ambliopia anisometrópica: relato de caso

The aim of this study is to report a clinical case of asymptomatic female Caucasian children with torpedo maculopathy. A 5-year-old girl was referred to our clinic for routine evaluation. The ophthalmic examination revealed best-corrected visual acuity of 20/20 in both eyes, without any changes in the biomicroscopy. Fundus examination showed normal findings in one eye, whereas in the contralateral eye it disclosed, in the temporal sector of the macular region, a whitish, atrophic, oval chorioretinal lesion with clearly defined margins. Posterior evaluations documented the stability of the lesion. Torpedo maculopathy diagnosis is based on its characteristic shape and peculiar location. The differential diagnosis has to be estabilished versus choroidal lesions (melanoma and nevus), congenital or iatrogenic hyperplasia of the retinal pigment epithelium (RPE) and particularly versus the congenital pigmented lesions associated with Gardner's syndrome.

Os autores descrevem um caso clínico de uma criança caucasiana, 5 anos do sexo feminino, com maculopatia torpedo. Ao exame oftalmológico apresentava uma acuidade visual corrigida de 10/10 e sem alterações à biomicroscopia. À fundoscopia apresentava uma lesão oval isolada, esbranquiçada, atrófica, unilateral, de margens bem definidas no setor temporal da região macular. Avaliações posteriores documentaram a estabilidade da lesão. O diagnóstico da maculopatia torpedo baseia-se na sua forma característica e localização peculiar. É importante o diagnóstico diferencial com lesões da coroideia (melanoma e nevo), hiperplasias congênitas ou iatrogênicas do epitélio pigmentado da retina (EPR) e com lesões congênitas associadas à síndrome de Gardner.

Bilateral acute depigmentation of the iris (BADI): first reported case in Brazil / Despigmentação aguda bilateral da íris (BADI): primeiro relato de caso no Brasil

Bilateral acute depigmentation of the iris (BADI) is a recently described entity characterized by acute onset of pigment dispersion in the anterior chamber, depigmentation of the iris, and heavy pigment deposition in the anterior chamber angle. Involvement is always bilateral, simultaneous, and symmetrical. We report the case of a 61-year-old man who presented with bilateral ocular pain, red eyes, and severe photophobia. Examination revealed a dense Krukenberg spindle, heavy pigment dispersion in the anterior chamber, extensive transillumination iris defects, and a heavy pigment deposition in the trabecular meshwork bilaterally. Intraocular pressure increased to 48 mmHg in both eyes. The patient received topical steroids, maximum hypotensive treatment and oral valacyclovir. Intraocular pressure gradually decreased throughout the second and third months, and medications were gradually tapered. The time to complete resolution of pigment dispersion was 18 weeks. Visual acuity and visual fields remained normal, but the photophobia was permanent.

Despigmentação aguda bilateral da íris (BADI) é uma nova doença caracterizada pela despigmentação aguda da íris, dispersão de pigmentos na câmara anterior e intensa deposição de pigmentos no seio camerular. O acometimento é sempre bilateral, simultâneo e simétrico. Relatamos o caso de um paciente de 61 anos, com dor ocular bilateral aguda, hiperemia e intensa fotofobia. Ao exame, apresentava denso fuso de Krukenberg, importante dispersão de pigmentos na câmara anterior, extensos defeitos à transiluminação iriana e densa deposição de pigmentos no seio camerular em ambos os olhos. O paciente recebeu corticoide tópico, terapia hipotensora máxima e valacyclovir oral. A pressão intraocular chegou a 48 mmHg em ambos os olhos mas foi reduzindo gradativamente ao longo do segundo e terceiro meses, permitindo a suspensão gradativa da medicação. A resolução completa da dispersão pigmentar demorou 18 semanas. A acuidade e os campos visuais permaneceram normais, mas o paciente manteve a fotofobia.