Analysis of Changes in Retinal Photoreceptors Using Optical Coherence Tomography in a Feline Model of Iodoacetic Acid-induced Retinal Degeneration

PURPOSE: We investigated structural changes in the retina by using optical coherence tomography (OCT) in a feline model of retinal degeneration using iodoacetic acid (IAA).METHODS: We examined 22 eyes of 11 felines over 2 years of age. The felines had fasted for 12 hours and were intravenously injected with IAA 20 mg/kg of body weight. OCT (Spectralis OCT) was performed at the point where the ends of the retinal vessels collected in the lateral direction from the optic nerve head and area centralis. Similarly, OCT was performed four times at 1-week intervals following injections, at which point the felines were sacrificed and histologic examinations were performed. Using OCT, the thickness of each layer of the retina was measured.RESULTS: The average body weight of the three male and eight female felines investigated in this study was 1.61 ± 0.19 kg. The mean total retinal thickness of the felines before injection was 221.32 ± 9.82 µm, with a significant decrease in the retinal thickness at 2, 3, and 4 weeks following injections of 186.41 ± 35.42, 174.56 ± 31.94, and 175.35 ± 33.84 µm, respectively (p = 0.028, 0.027, and 0.027, respectively). The thickness of the outer nuclear layer was 57.49 ± 8.03 µm before injection and 29.26 ± 17.87, 25.62 ± 13.88, and 31.60 ± 18.38 µm at 2, 3, and 4 weeks, respectively, after injection (p = 0.028, 0.028, 0.046, respectively).CONCLUSIONS: In a feline model of retinal degeneration using IAA, the total retinal thickness and the thickness of the outer nuclear layer were shown to decrease significantly on OCT.

Generation of Retinal Progenitor Cells from Human Induced Pluripotent Stem Cell-Derived Spherical Neural Mass

Spherical neural mass (SNM) is a mass of neural precursors that have been used to generate neuronal cells with advantages of long-term passaging capability with high yield, easy storage, and thawing. In this study, we differentiated neural retinal progenitor cells (RPCs) from human induced pluripotent stem cells (hiPSC)-derived SNMs. RPCs were differentiated from SNMs with a noggin/fibroblast growth factor-basic/Dickkopf-1/Insulin-like growth factor-1/fibroblast growth factor-9 protocol for three weeks. Human RPCs expressed eye field markers (Paired box 6) and early neural retinal markers (Ceh-10 homeodomain containing homolog), but did not photoreceptor marker (Opsin 1 short-wave-sensitive). Reverse transcription polymerase chain reaction revealed that early neural retinal markers (Mammalian achaete-scute complex homolog 1, mouse atonal homolog 5, neurogenic differentiation 1) and retinal fate markers (brain-specific homeobox/POU domain transcription factor 3B and recoverin) were upregulated, while the marker of retinal pigment epithelium (microphthalmia-associated transcription factor) only showed slight upregulation. Human RPCs were transplanted into mouse (adult 8 weeks old C57BL/6) retina. Cells transplanted into the mouse retina matured and expressed markers of mature retinal cells (Opsin 1 short-wave-sensitive) and human nuclei on immunohistochemistry three months after transplantation. Development of RPCs using SNMs may offer a fast and useful method for neural retinal cell differentiation.

Solar Retinopathy with Interesting Imaging Findings. A Case Report

Solar retinopathy is an injury of the retinal photoreceptors due to excessive exposure to the solar radiation. Diagnosis of the disease is challenging and requires combination of a detailed history and imaging modalities. This case report focuses on a 55-year-old fruit picker with an irreversible central scotoma of the right eye. A diagnosis of solar retinopathy was made based on history but mainly by several imaging modalities, such as optical coherence tomography (OCT), infrared (IF) imaging of the fundus and fundus autofluorescence (FAF). Electroretinogram (ERG)showed flattened and reduced waves in both scotopic and photopic response. Fundus angiography (FA) revealed no obvious telangectatic vessels. In conclusion, solar retinopathy is a disease where multimodal imaging may play an important role in the diagnosis. The condition may be irreversible thus advocating protective eyewear is mandatory in patients who are chronically exposed to the sun.

A Case of Transient Color Anomaly and Persistent Visual Field Defect after Sildenafil Citrate Overdose

PURPOSE: Sildenafil citrate, is an oral tablet demonstrating efficacy for maintaining an erection in males with erectile dysfunction by inhibiting phosphodiesterase type 5 (PDE5). In the present study, we report 1 case of a transient color anomaly with visual field defect after an overdose of sildenafil citrate. CASE SUMMARY: One patient, a 39-year-old female, with no significant medical history other than previous major depressive disorder, visited an outpatient department due to the visual field defect that began after taking 30 tablets of sildenafil citrate (50 mg) 3 days earlier. A number of ophthalmologic tests were administered including visual acuity test, color vision test, fundus photography and the measurement of retinal structure with optical coherent tomography and her condition was monitored. The best corrected visual acuity was 1.0 in both right and left eyes in her first visit. The color anomaly and a central scotoma of both eyes were detected in the visual field test, while significant signs were not observed after evaluation using optical coherent tomography and fundus photography. After 5 weeks, the visual acuity was not affected, the color anomaly symptom disappeared and the focal visual field defect was present although improved. CONCLUSIONS: Transient color anomaly and persistent central scotoma caused by an overdose ingestion of sildenafil has not been reported in Korea, The related mechanisms may involve the inhibition of PDE5 on ganglion cells and bipolar cells in the retina and interruption of phosphodiesterase type 6 (PDE6) function in both rods and cones.

A Case of Oxaliplatin-Related Ocular Toxicity

PURPOSE: To report a case of oxaliplatin (Eloxatin(R))-related ocular toxicity in a patient with advanced stomach cancer. CASE SUMMARY: A 43-year-old female with advanced stomach cancer experienced visual symptoms during the treatment with oxaliplatin on a XELOX schedule (a combination of oxaliplatin and capecitabine). After 1 cycle of chemotherapy, she complained of blurred vision and visual field defects in both eyes. Visual field tests showed a bilateral concentric field defect and the electroretinogram revealed a marked reduction of responses in both eyes. On the second cycle of chemotherapy, oxaliplatin was discontinued due to suspicious ocular toxicity. Her visual symptoms improved and visual field test showed normal results 1 month after oxaliplatin discontinuation. However, 3 months after oxaliplatin discontinuation, electroretinogram remained abnormal despite the progressive improvement. CONCLUSIONS: Platinum-based antineoplastic agents such as oxaliplatin should be administered with caution because oxaliplatin can cause damage to the retinal photoreceptors and the optic nerve. Early detection of ocular toxicity and discontinuation of oxaliplatin therapy could prevent severe and irreversible visual loss.

Effect and mechanisms of wenyang yiqi huoxue recipe on the apoptosis of photoreceptor cells in retinal degeneration slow mice / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of Wenyang Yiqi Huoxue Recipe (WYHR) on the apoptosis of photoreceptor cells in retinal degeneration slow (RDS) mice, and to investigate its molecular mechanisms.</p><p><b>METHODS</b>RDS mice were randomly divided into the model group and the Chinese medicine group,and C57BL/6J mice were selected as the normal control group. Each group consisted of 4 female mice and 2 male mice. Mice in the Chinese medicine group were administered with WYHR (10 mg/g) by gastrogavage since mating. Baby mice drunk WYHR decoction instead of drinking water once they were born. The offspring were administrated with low dose WYHR decoction by gastrogavage from the 7th postnatal day, and the dose was increased to that for adult mice from the 21st postnatal day. Physiological saline was administrated to mice in the model group and the normal control group by gastrogavage. At 18, 28 and 48 postnatal days, electroretinogram (ERG) was used to evaluate the retina functional variation, and the apoptotic rate of photoreceptor cells was determined by TUNEL staining. HE staining was performed. The number of photoreceptor cells of the outer nuclear layer was calculated. Furthermore, effect of WYHR on Rhodopsin and basic fibroblast growth factor (bFGF) expression was examined using immunochemical assay.</p><p><b>RESULTS</b>Compared with the model group, a- and b-wave latency and amplitude, as well as the bFGF expression sharply increased in the Max-ERG of the Chinese medicine group (P < 0.05, P < 0.01) at 18 postnatal days. At 28 and 48 postnatal days, a- and b-wave latency and amplitude sharply increased, photoreceptor cell layer numbers of the outer nuclear layer obviously increased, the apoptosis rate of retinal photoreceptor cells obviously decreased, expressions of Rhodopsin and bFGF in the Chinese medicine group significantly increased (P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>WYHR could effectively inhibit the apoptosis of photoreceptor cells in RDS mice, which might be attributed to up-regulating bFGF expression.</p>

Comparing three methods of co-culture of retinal pigment epithelium with progenitor cells derived human embryonic stem cells

Close interaction between retinal pigment epithelium [RPE] and photoreceptors plays an essential role in visual function. The objective of this study is to determine the effects of RPE cells in the differentiation of progenitor derived human embryonic stem cells [hESC] into retinal cells; we developed in vitro co-culture models and compare these models to investigate in which model the expression of photoreceptor markers is superior. It seems the effects of RPE cells on differentiation of retinal progenitor cells [RPCs] through the cell-to-cell contact or with the use of insert and compare of these methods has not been reported yet. Initially, retinal progenitors [RPs] were differentiated from hESC. After isolation of RPE sheet from rabbit eyes, demonstrated these cells maintains the integrity and feature after 2 weeks. Next, we examined the induction of photoreceptors by the co-culture of RPE through insert in 1 week and 2 weeks [indirect] or without insert by the cell-to-cell contact [direct]. The differentiation of retinal cells was verified by protein and gene expression in these three methods. The adherent cells were morphologically examined using phase contrast microscopy and characterized by immunofluorescent staining and reverse transcription polymerase chain reaction [RT PCR]. Evaluation of immunostaining showed that hESC, highly [>80%] can be directed to the RPs fate. Upon co-culture of RPCs with RPE sheet using insert for 2 weeks or by the cell-to-cell contact, these cells differentiated to neural retina and expressed photoreceptor specific markers. However, in direct co-culture, some mature photoreceptor markers like arrestin expressed in compare with indirect co-culture. The expression of late photoreceptor marker could be improved when RPE cells seeded on RPCs in compare with the use of insert.

Experimental models of autoimmune inflammatory ocular diseases / Modelos experimentais para o estudo de doenças inflamatórias oculares autoimunes

Ocular inflammation is one of the leading causes of blindness and loss of vision. Human uveitis is a complex and heterogeneous group of diseases characterized by inflammation of intraocular tissues. The eye may be the only organ involved, or uveitis may be part of a systemic disease. A significant number of cases are of unknown etiology and are labeled idiopathic. Animal models have been developed to the study of the physiopathogenesis of autoimmune uveitis due to the difficulty in obtaining human eye inflamed tissues for experiments. Most of those models are induced by injection of specific photoreceptors proteins (e.g., S-antigen, interphotoreceptor retinoid-binding protein, rhodopsin, recoverin, phosducin). Non-retinal antigens, including melanin-associated proteins and myelin basic protein, are also good inducers of uveitis in animals. Understanding the basic mechanisms and pathogenesis of autoimmune ocular diseases are essential for the development of new treatment approaches and therapeutic agents. The present review describes the main experimental models of autoimmune ocular inflammatory diseases.

A inflamação ocular é uma das principais causas de perda visual e cegueira. As uveítes constituem um grupo complexo e heterogêneo de doenças caracterizadas por inflamação dos tecidos intraoculares. O olho pode ser o único órgão envolvido ou a uveíte pode ser parte de uma doença sistêmica. A etiologia é desconhecida em um número significativo de casos, que são considerados idiopáticos. Modelos animais têm sido desenvolvidos para estudar a fisiopatogênese da uveíte autoimune devido às dificuldades na obtenção de tecidos de olhos humanos inflamados para experimentos. Na maioria desses modelos, que simulam as uveítes autoimunes em humanos, a uveíte é induzida com proteínas específicas de fotorreceptores (antígeno-S, proteína ligadora de retinoide do interfotoreceptor, rodopsina, recoverina e fosducina). Antígenos não retinianos, como proteínas associadas à melanina e proteína básica de mielina, são também bons indutores de uveíte em animais. Entender os mecanismos básicos e a patogênese dessas doenças oculares é essencial para o desenvolvimento de novas formas de tratamento das uveítes autoimunes e de novos agentes terapêuticos. Nesta revisão serão abordados os principais modelos experimentais utilizados para o estudo de doenças inflamatórias oculares autoimunes.

Characterization of Peripapillary Atrophy Using Spectral Domain Optical Coherence Tomography

PURPOSE: To characterize the features of peripapillary atrophy (PPA), as imaged by spectral-domain optical coherence tomography (SD-OCT). METHODS: SD-OCT imaging of the optic disc was performed on healthy eyes, eyes suspected of having glaucoma, and eyes diagnosed with glaucoma. From the peripheral beta-zone, the retinal nerve fiber layer (RNFL), the junction of the inner and outer segments (IS/OS) of the photoreceptor layer, and the Bruch's membrane/retinal pigment epithelium complex layer (BRL) were visualized. RESULTS: Nineteen consecutive eyes of 10 subjects were imaged. The RNFL was observed in the PPA beta-zone of all eyes, and no eye showed an IS/OS complex in the beta-zone. The BRL was absent in the beta-zone of two eyes. The BRL was incomplete or showed posterior bowing in the beta-zone of five eyes. CONCLUSIONS: The common findings in the PPA beta-zone were that the RNFL was present, but the photoreceptor layer was absent. Presence of the BRL was variable in the beta-zone areas.

Central Photoreceptor Viability and Prediction of Visual Outcome in Patients with Idiopathic Macular Holes

PURPOSE: To identify the correlation between preoperative optical coherence tomography (OCT) features and postoperative visual outcomes in eyes with idiopathic macular holes (MHs). METHODS: Data from 55 eyes with idiopathic MHs which had been sealed by vitrectomy were retrospectively reviewed. Correlation analysis was conducted between postoperative visual acuity (V(postop), logarithm of the minimum angle of resolution [logMAR]) and preoperative factors, including four OCT parameters: the anticipated length (A) devoid of photoreceptors after hole closure, MH height (B), MH size (C), and the grading (D) of the viability of detached photoreceptors. Additionally, the formula for the prediction of visual outcome was deduced. RESULTS: V(postop) was determined to be significantly correlated with the preoperative visual acuity (V(preop)) and OCT parameters A, C, and D (p<0.001). Based on the correlation, the formula for the prediction of V(postop) was derived from the most accurate regression analysis: V(postop)=0.248xV(preop)+1.1x10(-6)xA(2)-0.121xD+0.19. CONCLUSIONS: The length and viability of detached photoreceptors are significant preoperative OCT features for predicting visual prognosis. This suggests that, regardless of the MH size and symptom duration, active surgical intervention should be encouraged, particularly if the MH exhibits good viability in the detached photoreceptor layer.

Edema of the Photoreceptor Layer in Vogt-Koyanagi-Harada Disease Observed Using High-Resolution Optical Coherence Tomography

PURPOSE: To evaluate the characteristics of fluid accumulation in the uveitic stage of Vogt-Koyanagi-Harada (VKH) disease using high resolution optical coherence tomography (OCT3). METHODS: Twenty-eight eyes in 14 patients with VKH disease were reviewed retrospectively. These 28 eyes were divided into 19 eyes with intraretinal fluid (C group) and 9 eyes without intraretinal fluid (N group). Changes in visual acuity and fluid accumulation observed using OCT were compared between the two groups. RESULTS: Visual acuity at the time of presentation was significantly worse in the C group than in the N group (p=0.005). The photoreceptor layer appeared to be double-layered due to a cystoid space in the C group. Layered structures and strands found in the cystoid space. Expanding sponge-form edema led to the development of a cystoid space in the photoreceptor layer. Intraretinal fluid resolved earlier than subretinal fluid. There were no observed differences in visual acuity between the two groups after four days of treatment. CONCLUSIONS: Accumulation of intraretinal fluid was related to poor initial visual acuity, but not to final visual acuity. High resolution OCT findings indicate that edema of the photoreceptor layer participates in the development of a cystoid space.

La evolución de los ojos / The evolution of the eyes

La evolución de los ojos comenzó cuando comenzó la vida misma. Incluso las formas de vida más simples, las bacterias, tienen las primeras proteínas fotosensibles. Desde las bacterias la vida y la visión evolucionaron hacia una asombrosa variedad y complejidad: ojos telescópicos, ojos especulares, ojos tipo cámara, todos ellos con un solo origen.

The evolution ofthe eyes began when the life itself began. Even the simplest life forms, the bacteria, have the first photosensitive proteins. From the bacteria, the life and the vision evolved towards an astonishing variety and complexity: telescope eyes, mirror eyes, camera eyes, between many others, all ofthem with a single source.

Ophthalmologic Findings of Boucher-Neuhauser Syndrome

To report a case of Boucher-Neuhauser syndrome, which is an autosomal recessive disorder characterized by the triad of spinocerebellar ataxia, chorioretinal dystrophy, and hypogonadotropic hypogonadism. An 18-year-old man was seen for visual problems, which had been diagnosed as retinitis pigmentosa at the age of 12 years. His puberty was delayed. At 16 years of age, the patient experienced progressive deterioration of his balance and gait disturbance. Then he was referred to our clinic because Boucher-Neuhauser syndrome was suspected. He had no specific family history; his visual acuity was 0.04 in both eyes. We observed broad retinal pigment epithelium atrophy and degeneration in both fundi. Both fluorescein and indocyanine green angiography showed choriocapillaris atrophy in the posterior pole area and midperiphery. Macular optical coherence tomography showed thinning of the neurosensory retina. An electroretinographic examination showed no photopic or scotopic responses. The Boucher-Neuhauser syndrome should be included in the differential diagnosis of patients with retinitis pigment epithelium atrophy and degeneration.

Reorganization of Photoreceptor Layer on Optical Coherence Tomography Concurrent with Visual Improvement after Macular Hole Surgery

To report three cases in which reorganization of the photoreceptor layer on optical coherence tomography (OCT) was concurrent with long-term visual recovery after macular hole surgery. Serial OCT scans of three eyes in which visual acuity continued to improve for 1 or more years after successful macular hole surgery were reviewed. Case 1. At postoperative four weeks, visual acuity was 20/100 with disorganized photoreceptor layer on OCT. The photoreceptor layer had been reorganized and visual acuity had improved to 20/25 by 1 year. Case 2. Two weeks after the operation, visual acuity was 20/125 and disorganization of the photoreceptor layer was noted. Visual acuity improved to 20/50 by four months. The photoreceptor layer had been partly reorganized and had appearance of a broken line. Visual acuity had improved to 20/40 and the photoreceptor layer had been reorganized further with a residual defect on OCT by 15 months. Case 3. Visual acuity at two weeks was 20/100. OCT revealed disorganization of the photoreceptor layer. Six months after the operation, the partly reorganized photoreceptor layer appeared as a broken line and visual acuity had reached 20/80. Visual acuity had improved further to 20/40 by 1 year, concurrent with improved organization of the photoreceptor layer. The reorganization of the photoreceptor layer plays a part in long-term improvement of visual acuity after macular hole surgery.

A Novel Mutation in the XLRS1 Gene in a Korean Family with X-linked Retinoschisis

PURPOSE: To report a novel missense mutation in the XLRS1 gene in a Korean family with X-linked retinoschisis. METHODS: Observation case report of a family with a proband with X-linked retinoschisis underwent complete ophthalmologic examination. Genomic DNA was excluded from the family's blood and all exons of the XLRS1 gene were amplified by polymerase chain reaction and analyzed using a direct sequencing method. RESULTS: A novel Leu103Phe missense mutation was identified. CONCLUSIONS: A novel Leu103Phe mutation is an additional missense mutation which is responsible for the pathogenesis of X-linked retinoschisis.

Circadian rhythms and different photoresponses of Clock gene transcription in the rat suprachiasmatic nucleus and pineal gland / 生理学报

The aim of this study was to observe and compare the endogenous circadian rhythm and photoresponse of Clock gene transcription in the suprachiasmatic nucleus (SCN) and pineal gland (PG) of rats. With free access to food and water in special darkrooms, Sprague-Dawley rats were housed under the light regime of constant darkness (DD) for 8 weeks (n=36) or 12 hour-light: 12 hour-dark cycle (LD) for 4 weeks (n=36), respectively. Then, their SCN and PG were dissected out every 4 h in a circadian day, 6 rats at each time (n=6). All animal treatments and sampling during the dark phases were conducted under red dim light (<0.1 lux). The total RNA was extracted from each sample and the semi-quantitative RT-PCR was used to determine the temporal mRNA changes of Clock gene in the SCN and PG at different circadian times (CT) or zeitgeber times (ZT). The grayness ratio of Clock/H3.3 bands was served as the relative estimation of Clock gene expression. The experimental data were analyzed by the Cosine method and the Clock Lab software to fit original results measured at 6 time points and to simulate a circadian rhythmic curve which was then examined for statistical difference by the amplitude F test. The main results are as follows: (1) The mRNA levels of Clock gene in the SCN under DD regime displayed the circadian oscillation (P<0.05). The endogenous rhythmic profiles of Clock gene transcription in the PG were similar to those in the SCN (P>0.05) throughout the day with the peak at the subjective night (CT15 in the SCN or CT18 in the PG) and the trough during the subjective day (CT3 in the SCN or CT6 in the PG). (2) Clock gene transcription in the SCN under LD cycle also showed the circadian oscillation (P<0.05), and the rhythmic profile was anti-phasic to that under DD condition (P<0.05). The amplitude and the mRNA level at the peak of Clock gene transcription in the SCN under LD were significantly increased compared with that under DD (P<0.05), while the value of corresponding rhythmic parameters in the PG under LD were remarkably decreased (P<0.05). (3) Under LD cycle, the circadian profiles of Clock gene transcription induced by light in the PG were quite different from those in the SCN (P<0.05). Their Clock transcription rhythms were anti-phasic, i.e., showing peaks at the light phase ZT10 in the SCN or at the dark time ZT17 in the PG and troughs during the dark time ZT22 in the SCN or during the light phase ZT5 in the PG. The findings of the present study indicate a synchronous endogenous nature of the Clock gene circadian transcriptions in the SCN and PG, and different roles of light regime in modulating the circadian transcriptions of Clock gene in these two central nuclei.

Acuidade visual e eletrorretinografia de campo total em pacientes com síndrome de Usher / Visual acuity and full-field electroretinography in patients with Usher's syndrome

A síndrome de Usher (SU) é doença autossômica recessiva caracterizada por perda auditiva neuro-sensorial acompanhada de retinose pigmentária (RP). OBJETIVO: Analisar a eletrorretinografia de campo total (ERG) e a acuidade visual (AV) em pacientes com síndrome de Usher tipos I e II. MÉTODOS: Foram estudadas as respostas da eletrorretinografia de campo total e a acuidade visual de 22 pacientes (idade média = 26,8±16,8 anos). Destes, 17 tinham síndrome de Usher tipo I e 5 tinham síndrome de Usher tipo II. RESULTADOS: A acuidade visual média do grupo síndrome de Usher I foi de 0,9 logMAR (20/160, equivalente de Snellen) e do grupo síndrome de Usher II de 0,4 logMAR (20/50, equivalente de Snellen). As respostas dos bastonetes e as máximas respostas mostraram-se não detectáveis nos dois grupos. A amplitude média dos potenciais oscilatórios foi de 14,5 µV±6,1 na síndrome de Usher I e na síndrome de Usher II de 12,6 µV±5,2. As respostas de cones foram não detectáveis em 95 por cento dos pacientes com síndrome de Usher I e em 100 por cento dos pacientes com síndrome de Usher II. A amplitude média do flicker a 30 Hz nos pacientes com síndrome de Usher I foi de 3,1 µV±4,1 e do tempo de culminação de 34,0ms±6,2; nos pacientes com síndrome de Usher II a média de amplitude foi de 1,0 mV±0,6 e do tempo de culminação de 35,8 ms±3,1. CONCLUSAO: A acuidade visual mostrou-se relativamente preservada nos dois grupos, porém com melhores resultados no grupo de síndrome de Usher II. Os achados eletrorretinográficos mostraram-se grandemente reduzidos em ambos os grupos, com a maioria dos pacientes apresentando respostas não detectáveis de bastonetes e cones.

Protective effect of non-mitogenic haFGF on retinal injury induced by N-methyl-N-nitrosourea in Sprague-Dawley rats / 药学学报

<p><b>AIM</b>To study the effect of non-mitogenic human acidic fibroblast growth factor (nm-haFGF) on retinal injury induced by N-methyl-N-nitrosourea (MNU) in Sprague-Dawley rats and its mechanism.</p><p><b>METHODS</b>Female rats of 50-days-old were injected with MNU (60 mg x kg(-1)) intraperitoneally, and three doses of nm-haFGF (1.25 microg, 2.5 microg and 5 microg in one eye of each rat) were injected, separately, into vitreous body of one eye of each rat twice a day at 0 and 12 h after MNU treatment. 24 h later, apoptotic index of photoreceptor cells was detected by TUNEL labeling and the expressions of Bcl-2 and Bax were analyzed by Western blotting. At the 7th day, retinal injury was evaluated based on retinal thickness.</p><p><b>RESULTS</b>Compared with model group, apoptotic index of photoreceptor cells was significantly reduced in nm-haFGF groups at the dose of 1.25 microg and 2.5 microg in one eye of each rat at 24 h, and the total retinal thickness as well as the outer retinal thickness markedly increased 7 days after MNU, respectively. The expressions of Bcl-2 increased and that of Bax decreased adversely after being injected with different doses of nm-haFGF.</p><p><b>CONCLUSION</b>nm-haFGF partially suppressed retinal injury induced by MNU in Sprague-Dawley rats. The mechanism could be related to up-regulation of Bcl-2 and down-regulation of Bax.</p>

Protective effects of ligustrazine against photoreceptor cell injury induced by N-methyl-N-nitrosourea and its mechanism / 药学学报

<p><b>AIM</b>To study the protective effect of ligustrazine against photoreceptor cell injury induced by N-methyl-N-nitrosourea (MNU) in Sprague-Dawley (SD) rats.</p><p><b>METHODS</b>Ligustrazine injections of different doses were injected intraperitoneally into 47-day female SD rats once a day and a single intraperitoneal injection of MNU 60 mg x kg(-1) was given to 50-day rats. At different intervals after MNU treatment,the animals were sacrificed. The apoptotic index of photoreceptor cells was calculated by TUNEL labeling at 24 h following MNU treatment; peripheral retinal damage was evaluated based on retinal thickness at the d 7 after MNU treatment, and the expression of c-jun and c-fos genes was detected by RT-PCR technique.</p><p><b>RESULTS</b>Ligustrazine injection could remarkably increase total thickness of peripheral retina and decrease apoptotic index of photoreceptor cells induced by MNU in a dose-dependent manner. Compared with MNU-treated rats, the gene expression of c-jun and c-fos was time-dependently down-regulated in ligustrazine-treated group.</p><p><b>CONCLUSION</b>Ligustrazine injection partially protects against MNU-induced retinal damage by down-modulating the expression of c-jun and c-fos genes to inhibit apoptosis of photoreceptor cells.</p>

Delay of Photoreceptor Cell Degeneration in rd Mice by Systemically Administered Phenyl-N-tert-butylnitrone

PURPOSE: To study the effect of systemic administration of phenyl-N-tert-butylnitrone (PBN) on the degeneration of photoreceptor cells in rd mice. METHODS: PBN was injected intraperitoneally into FVB/rd mice on postnatal days (P) 5 to 14 (group A), and P10 to 18 (group B). At days P14, 16, 18, 20 and 27, morphological changes and apoptosis were analyzed by staining with hematoxylin and eosin or DAPI. The effect of PBN on apoptosis was analyzed in retinal pigment epithelial (RPE) cells by the measurement of caspase-3 activity. RESULTS: In control and group B mice, the outer nuclear layer (ONL) of the retina was composed of 8-10 rows at P12, and rapidly decreased to one row at P18. In group A mice, the ONL was preserved with 5-7 rows at P18, and decreased to one row at P22. PBN inhibited caspase-3 activity in cultured RPE cells. CONCLUSIONS: PBN delayed, but did not block, the degeneration of photoreceptor cells in rd mice. PBN may exert its inhibitory effect during the early phase of photoreceptor cell degeneration.