The Beneficial Effects of Photobiomodulation to Reduce Intraocular Pressure in Primary Open-Angle Glaucoma

Purpose: The aim of this trail was to study the efficacy of photobiomodulation (PBM) treatment to reduce the intraocular pressure in subjects with primary open angle glaucoma disease.Methods: Twenty eyes suffering from open angle glaucoma with high IOP level were selected, examined and treated with Thera-RED light diode system. The subjects were divided into two groups (n=10); treated and placebo group respectively; this system provide two lights (red at 660n.m continue and Near IR light micro-pulsed at 850 n.m), the patients received two series of treatment (ten per month within three months between every series of sessions) over five months and follow up taking ocular pressure measurements after every diode delivery session.Results: A significant decrease in IOP has been observed from the first month of the treatment compared to the placebo group (from 22.6mmHg before treatment to 15 mmHg after the tenth session) this amelioration has been also remarked during the second session of treatment (fifth month) to attempt 14.2 mmHg. Conclusion: Thera-RED light diode system treatment shows a significant decrease of IOP and remained to be stable under 14.2 mmHg in all the follow up, which confirm that photobiomodulation help in reducing the intraocular pressure in glaucomatous patients .

Search for potential target genes in dexamethasone-induced open-angle glaucoma by bioinformatics / 中华实验眼科杂志

Objective:To predict potential target genes in dexamethasone-induced open-angle glaucoma via bioinformatics technology.Methods:The GEO datasets GSE16643, GSE37474, and GSE124114 were used to analyze the differentially expressed genes by GEO2R.Gene Set Enrichment Analysis (GSEA) was performed on the differentially expressed genes between GSE37474 and GSE124114.Intersection of the three datasets were displayed by Venn diagram.The annotation and enrichment analysis of the intersection genes were performed through Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and then were compared with normal tissue in GTEx Portal database.The corresponding protein interaction network was obtained by STRING.Finally, the candidate genes were searched for their transcription factors in UCSC and JASPAR.Primary human trabecular cells were divided into dexamethasone group and control group, treated with 2 ml 500 nmol/L dexamethasone and the same amount of ethanol, respectively.The expression of BDKRB1 and TAGLN in trabecular cells was detected by Western blot.Results:Differential genes between GSE37474 and GSE124114 datasets enriched in complement and coagulation cascade by GSEA.There were 89 intersecting genes of the three datasets.These genes mainly regulated the formation of extracellular matrix by GO analysis.The gene with the highest enrichment score and collagen-containing extracellular matrix was found to be associated with fibroblasts in GTEx Portal database.ACTA2, MYL9, TAGLN, and LMOD1 were closely related in STRING protein-protein interaction network.Transcription factor SP1 in UCSC and JASPAR according to related genes, BDKRB1, NID1, MFGE8 and TAGLN.The relative expression levels of BDKRB1 and TAGLN proteins were 1.32±0.14 and 0.44±0.09 in dexamethasone group, respectively, which were significantly higher than 1.00±0.00 and 0.20±0.10 in the control group, respectively ( t=-3.61, 2.89; both at P<0.05). Conclusions:Bioinformatics analysis showed that transcription factor SP1 may play a role in human trabecular meshwork cells to myofibroblasts transition after dexamethasone treatment.

Anti-inflammatory treatment after selective laser trabeculoplasty: a systematic review of the literature and meta-analysis of randomized control trials / Tratamento anti-inflamatório após trabeculoplastia seletiva a laser: revisão sistemática da literatura e meta-análise de ensaios clínicos randomizados controlados

ABSTRACT We assessed the effects of anti-inflammatory treatment after selective laser trabeculoplasty through a systematic search of the MEDLINE, COCHRANE, and ClinicalTrials.gov. The outcome measures were intraocular pressure, anterior chamber inflammation, and discomfort. Evidence synthesis was performed using fixed effects or random-effects model according to the heterogeneity of the included studies. Heterogeneity was assessed using Q-statistic and I2. For an overall estimate of continuous outcomes, the mean differences and their 95% confidence intervals were applied, while odds ratios and their 95% confidence intervals were applied for dichotomous outcomes. Six studies were included in all. No significant difference was noted in the patients for intraocular pressure and discomfort when treated with anti-inflammatory drops. However, the patients showed benefit from reduced anterior chamber inflammation in the first postoperative week [FE OR=0.43, 95% CI=(0.19, 0.95), PQ=0.97, I2=0%], with no significant difference between the outcomes of non-steroidal anti-inflammatory drugs and steroids [FE OR=0.75, 95% CI=(0.20, 2.82), PQ=0.37, I2=0%]. Anti-inflammatory drops reduce anterior chamber inflammation after selective laser trabeculoplasty but showed no effect on the intraocular pressure.

RESUMO O objetivo deste estudo é avaliar os efeitos do tratamento anti-inflamatório após a trabeculoplastia seletiva a laser. Uma busca sistemática foi feita no MEDLINE, COCHRANE e ClinicalTrials.gov. As medidas de resultado foram pressão intraocular, inflamação da câmara anterior e desconforto. A síntese de evidência foi realizada utilizando-se modelo de efeitos fixos ou efeitos aleatórios, de acordo com a heterogeneidade dos estudos incluídos. A heterogeneidade foi avaliada utilizando-se Q-statistic e I². Para uma estimativa global dos resultados contínuos, foram usadas diferenças médias e seus intervalos de confiança de 95% enquanto para resultados dicótomos, usou-se odds ratios e seus intervalos de confiança de 95%. Seis estudos foram incluídos. Nenhuma diferença significativa foi encontrada em pacientes tratados com gotas anti-inflamatórias em termos de pressão intraocular e desconforto. No entanto, eles se beneficiaram da redução da inflamação da câmara anterior na primeira semana pós-operatória [FE OR=0,43, IC 95% = (0,19, 0,95), PQ=0,97, I2=0%], sem diferença significativa entre anti-inflamatórios não esteroidais e esteroidais [FE OR=0,75, IC 95% = (0,20, 2,82), PQ=0,37, I2=0%]. Gotas anti-inflamatórias reduzem a inflamação da câmara anterior após trabeculoplastia seletiva a laser, não afetando a pressão intraocular.

Gonioscopy-assisted transluminal trabeculotomy: Passing the right way decoding suture

Background: Trabeculectomy is still the most frequently performed glaucoma surgery. But being an invasive procedure, it has numerous vision?threatening complications along with bleb?related complications like cystic bleb, overhanging bleb blebitis, or endophthalmitis. The choice of therapy between medical laser and filtering surgery is now bridged by minimally invasive glaucoma surgeries (MIGS), which are conjunctiva?sparing procedures with adequate intraocular pressure (IOP)?lowering effects and good safety profiles. Among the armamentarium of MIGS procedures, gonioscopy?assisted transluminal trabeculotomy (GATT) is a frontrunner safe procedure. The procedure is a blebless and sutureless procedure in which a readily available Prolene suture is used to cleave the entire trabecular meshwork. An ab interno approach also allows direct visualization of a so?called trabecular shelf that, when present, indicates an open, cleaved collector system commonly associated with a positive postoperative outcome. Thus, it not only saves the eye from various postoperative complications of other previous penetrating procedures, but is also an effective glaucoma surgery that can be performed with very low costs, which would have big economic implications for glaucoma carein developing countries. Purpose: The purpose of this video is to illustrate transluminal novel trabeculotomy technique and video?based skill transfer to a novice surgeon. Synopsis: This video depicts detailed steps of GATT surgery in a patient with primary open angle glaucoma and in a case of silicon oil induced secondary open angle glaucoma. The authors also share their experience regarding possible intraoperative problems and solutions with some tips and tricks to make the surgery easy. Highlights: GATT can be performed with cataract surgery with minimal patient morbidity and a short recovery time with preserving healthy conjunctiva. There is no risk of post op hypotony or bleb related complications, with a short surgical learning curve

Short-term endothelial cell density changes after gonioscopy-assisted transluminal trabeculotomy / Alterações de curto prazo na densidade celular endotelial associadas à trabeculotomia transluminal assistida por gonioscopia

ABSTRACT Purpose: To investigate the reduction in corneal endothelial cell density associated with gonioscopy-assisted transluminal trabeculotomy (GATT) in a short-term follow-up period. Methods: A retrospective analysis of the medical charts of patients with open-angle glaucoma who underwent gonioscopy-assisted transluminal trabeculotomy isolated or combined with phacoemulsification (phaco-gonioscopy-assisted transluminal trabeculotomy) was conducted. Patients who underwent phacoemulsification alone were included as controls. The endothelial cell density data (assessed using a specular microscope) before and at the first month after operation were collected and then compared. Results: Sixty-two eyes previously treated with gonioscopy-assisted transluminal trabeculotomy (gonioscopy-assisted transluminal trabeculotomy, n=39 eyes; phaco-gonioscopy-assisted transluminal trabeculotomy, n=23 eyes) fulfilled the inclusion criteria. The mean age of the study patients was 61.3 ± 18.4 years in the stand-alone gonioscopyassisted transluminal trabeculotomy group and 60.4 ± 11.9 in phaco-gonioscopy-assisted transluminal trabeculotomy group. Men comprised 66.6% of the patients in the isolated gonioscopyassisted transluminal trabeculotomy group and 56.5% of those in the phaco-gonioscopy-assisted transluminal trabeculotomy group. The mean visual field defects (mean deviation index) were -13.9 ± 9.2 and -10.3 ± 7.7 dB in the isolated gonioscopy-assisted and phaco-gonioscopy-assisted transluminal trabeculotomy groups, respectively. The patients in the former group presented a mean endothelial cell density reduction of 28.8 cells/mm² (1.31%; p=0.467). In the latter group, the mean endothelial cell density loss was 89.4 cells/mm² (4.36%; p=0.028). The control eyes (23 patients) presented a mean endothelial cell density change of 114.1 ± 159.8 cells/mm² (4.41%; p=0.505). The endothelial cell density reduction in the phaco-gonioscopy-assisted transluminal trabeculotomy group was not significantly different from that in the controls (p=0.81). Conclusions: Gonioscopy-assisted transluminal trabeculotomy appears to be a safe procedure for the corneal endothelial cell layer when performed either isolated or combined with cataract extraction in a short-term follow-up period.

RESUMO Objetivo: Investigar a redução na densidade celular endotelial corneana associada à trabeculotomia transluminal assistida por gonioscopia (GATT) em curto prazo. Métodos: Análise retrospectiva de prontuários médicos de pacientes com glaucoma de ângulo aberto que foram submetidos à trabeculotomia transluminal assistida por gonioscopia isolada ou combinada com facoemulsificação. Pacientes que foram submetidos à facoemulsificação isolada foram incluídos como controles. Dados da densidade celular endotelial corneana (avaliada através de microscópio especular) pré-operatória e ao primeiro mês pós-operatório foram coletados e comparados. Resultados: Sessenta e dois olhos que foram submetidos à trabeculotomia transluminal assistida por gonioscopia (trabeculotomia transluminal assistida por gonioscopia=39 olhos; faco com trabeculotomia transluminal assistida por gonioscopia=23 olhos) passaram pelos critérios de inclusão. A idade média dos pacientes estudados era 61,3 ± 18,4 anos no grupo trabeculotomia transluminal assistida por gonioscopia isolada e 60,4 ± 11,9 anos no grupo faco com trabeculotomia transluminal assistida por gonioscopia. Homens eram 66,6% do grupo trabeculotomia transluminal assistida por gonioscopia isolada e 56,5% do grupo faco com trabeculotomia transluminal assistida por gonioscopia. O defeito perimétrico médio (Mean Deviation) era -13,9 ± 9,2 dB e -10,3 ± 7,7 dB nos grupos trabeculotomia transluminal assistida por gonioscopia isolada e faco com trabeculotomia transluminal assistida por gonioscopia respectivamente. O grupo que fora submetido à trabeculotomia transluminal assistida por gonioscopia isolada apresentou redução média da densidade celular endotelial corneana de 28,8 células/mm² (1,31%; p=0,467). No grupo faco com trabeculotomia transluminal assistida por gonioscopia, a redução média da densidade celular endotelial corneana foi de 89,4 células/mm² (4,36%; p=0,028). Olhos controle (23 olhos) apresentaram redução média da densidade celular endotelial corneana de 114,1 ± 159,8 células/mm² (4,41%; p=0,505). A redução na densidade celular endotelial corneana no grupo faco com trabeculotomia transluminal assistida por gonioscopia não foi significativamente diferente do grupo controle (p=0,81). Conclusões: A trabeculotomia transluminal assistida por gonioscopia parece ser segura para a camada endotelial corneana em um curto prazo quando realizada de forma isolada ou combinada com cirurgia de catarata.

Glaucoma e óleo de silicone / Glaucoma and silicone oils

RESUMO O óleo de silicone é um importante tampão utilizado na retinopexia cirúrgica de casos graves de descolamento de retina. O aumento da pressão intraocular e o desenvolvimento de glaucoma secundário são frequentes complicações da sua utilização. A depender do período de aparecimento, diversos mecanismos justificam a ocorrência de tais complicações. Compreender os fatores de riscos e a patogênese do aumento da pressão intraocular associada a aplicação de óleo de silicone em cirurgia retiniana ajuda a orientar o tratamento adequado para cada paciente. O objetivo deste artigo é revisar a literatura sobre a patogenia, a incidência, os fatores de risco e o tratamento desta condição clínica.

ABSTRACT Silicone oil has been an important intraocular tamponade in retinopexy in cases of complicated retinal detachment surgery. The increase of intraocular pressure and development of secondary glaucoma are a known complication of its use. A variety of mechanisms have been proposed for the pathogenesis, depending on the onset. This article aims to review the literature about pathogenesis, the incidence and risk factors, as well as the treatment of this pathology.

Short-term results of ab-interno trabeculotomy using Kahook Dual Blade in patients with primary congenital glaucoma / Resultados de curto prazo da trabeculotomia ab-interno usando o Kahook Dual Blade em pacientes com glaucoma congênito primário

ABSTRACT The aim of this study is to present the results of ab-interno trabeculotomy using Kahook Dual Blade in patients with primary congenital glaucoma. An ab-interno trabeculotomy using a dual blade device was performed in three eyes of two patients with the diagnosis of primary congenital glaucoma. One of them in the left eye and the other patient in both eyes. In the first patient, an adequate response was achieved after the intraocular pressure reduced from 36 mmHg to 14 mmHg. The second patient did not respond adequately to the procedure, and high intraocular pressure levels persisted in both eyes after the procedure. The indication of Kahook Dual Blade ab-interno trabeculotomy in primary congenital glaucoma must be cautious and more studies are needed to establish its efficacy and the best indications. Seems that this procedure should not be indicated for primary congenital glaucoma treatment.

RESUMO O objetivo deste estudo é apresentar os resultados da trabeculotomia ab-interno com Kahook Dual Blade em pacientes com glaucoma congênito primário. Foi realizada trabeculotomia ab-interno com dispositivo de lâmina dupla em 3 olhos de 2 pacientes com diagnóstico de glaucoma congênito primário. Um deles no olho esquerdo e o outro paciente nos dois olhos. No primeiro paciente, houve resposta adequada uma vez que a pressão intraocular diminuiu de 36 mmHg para 14mmHg. O segundo paciente não respondeu adequadamente ao procedimento, mantendo altos níveis de pressão intraocular em ambos os olhos após o procedimento. A indicação da trabeculotomia ab-interno com o Kahook Dual Blade no glaucoma congênito primário deve ser cautelosa e são necessários mais estudos para estabelecer a eficácia e as melhores indicações. Parece que esse procedimento não deve ser indicado no tratamento do glaucoma congênito primário.

Research progress of autophagy in the pathogenesis of glaucoma / 中华实验眼科杂志

Glaucoma, a neurodegenerative disease characterized by progressive death of retinal ganglion cells (RGCs) and chronic axonal degeneration, is often associated with elevated intraocular pressure.Autophagy, which means self-eating, is a mechanism of cell degradation and recycling.Excessive autophagy or impaired autophagy may lead to cell dysfunction and even cell death.Recent studies have shown that autophagy is closely related to trabecular meshwork cell dysfunction, RGCs apoptosis and optic nerve degeneration caused by different factors, including oxidative stress, mechanical stimulation, high intraocular pressure, axon injury, genetic factors and so on.Regulating autophagy to protect RGCs may provide new ideas for glaucoma treatments.In this article, the definition and classification of autophagy, the regulation of autophagy, the role of autophagy in the process of oxidative stress and mechanical stimulation on the function of trabecular meshwork cells, and the impact of autophagy on RGCs under high intraocular pressure and RGCs axonal injury, the relationship between autophagy and apoptosis in RGCs, as well as the latest research results on autophagy and hereditary optic nerve degeneration, regulation of autophagy via gene and drug for the treatment of glaucoma were reviewed.

Research progress of trabecular meshwork cell oxidative stress in the pathogenesis of glaucoma / 国际眼科杂志(Guoji Yanke Zazhi)

@#<p>Glaucoma is a common irreversible blinding eye disease, pathological elevated intraocular pressure is the main clinical feature. The formation of intraocular pressure, related to aqueous circulation, will be pathologically elevated when the aqueous cycle is abnormal. Trabecular network, which plays a key role in maintaining normal intraocular pressure, is the main component of aqueous outflow channel. Imbalance of oxidative stress manifested as oxidation and antioxidant effects is a direct risk factor for elevated intraocular pressure in glaucoma. When it comes to the trabecular meshwork cells, a series of changes such as deposition and degeneration of extracellular matrix, autophagy and aging will eventually occur, and finally the dysfunction of trabecular meshwork cells and increased aqueous outflow resistance, causing intraocular pressure pathological elevated. In this paper, we reviewed the research progress on the relationship between oxidative stress in trabecular meshwork cells and the pathogenesis of glaucoma, in order to provide evidence for further research and reference for exploring the pathogenesis, prevention and treatment of glaucoma.

Calidad ósea en poblaciones contemporáneas. Análisis de la estructura trabecular calcánea en una muestra esqueletal / Bone Quality in Contem porary Populations. Calcaneal Trabecular Structure Analysis in a Skeletal Sample

Resumen Objetivo: La osteoporosis es una condición de relevancia a nivel epidemiológico en Argentina, así como en el resto del mundo. Si bien actualmente la herramienta diagnóstica más relevante es la densitometría ósea, los análisis radiológicos pueden aportar información, principalmente en lo referente a la calidad ósea. En ese sentido, nos proponemos evaluar la estructura trabecular calcánea de una población local. Métodos: El material para dicho estudio consistió en 91 calcáneos de esqueletos pertenecientes a una muestra esqueletal. Fueron analizados individuos adultos, de ambos sexos, mediante imágenes radiográficas, a fin de clasificar su estructura trabecular de acuerdo al índice propuesto por Jhamaria y col., en una escala de V (normal) a I (osteoporosis severa). Resultados: Las prevalencias estimadas fueron de 23,1% de osteoporosis (fases I y II), 16,5% de borderline (fase III) y 48,4% se clasificó como estructura trabecular normal (fases IV y V). En relación a la edad de los individuos, se encontró una correlación significativa negativa entre ella y la pérdida trabecular (tau-b = -0,524, p = 0,00). No se encontraron diferencias significativas en cuanto a la afección dimórfica de la patología. Discusión: La relación entre envejecimiento y osteoporosis hallada es coincidente con estudios nacionales e internacionales que reconocen una disminución en la densidad mineral ósea (DMO) y una mala calidad ósea en individuos adultos mayores. La ausencia de afección dimórfica podría deberse a la edad promedio de la muestra, sumada a la posible resistencia de la estructura esponjosa del calcáneo a los cambios generados por el déficit estrogénico en las mujeres, característica de la osteoporosis tipo I. Conclusión: Creemos que es necesario revalorizar el análisis óseo por medio de radiografías, puesto que pueden ser de utilidad tanto en la clínica como en la investigación básica, debido a la mayor disponibilidad de equipos y a que posibilitan el análisis de otras propiedades del tejido óseo.

Abstract Objective: Osteoporosis is an important condition in an epidemiologic level in Argentina as in the rest of the world. Even though nowadays the most relevant diagnostic technique is bone densitometry, radiological studies can provide useful information, mainly in relation to bone quality. For this purpose, we aim to evaluate the calcaneus trabecular structure in a contemporary local population. Methods: The sample for this study consisted of 91 calcaneus from skeletons belonging to the skeletal repository. Adult individuals from both sexes were analyzed, to classify their trabecular structure according to the index proposed by Jhamaria et al., on a scale of V (normal) to I (severe osteoporosis). Results: The estimated prevalence were 23,1% of osteoporosis (phase I and II), 16,5% of borderline (phase III) and 48,4% were classified as normal trabecular structure (phase IV and V). In relation to the age of the individuals, a significant negative correlation was found between the first and the trabecular loss (tau-b = -0.524, p = 0.00). No significant differences were found in relation to the sex prevalence of this pathology. Discussion: The association found between aging and osteoporosis matches with the results of national and international studies that recognize that a decrease in Bone Mineral Density (BMD) and a bad bone quality in older adults. Absence of differences between sexes in this condition could be due to age average of the sample, added to the possible resistance of the calcaneus spongy structure to changes generated by estrogen deficit in women, characteristic of osteoporosis type I. Conclusion: We believe that it is necessary to revalue bone analysis by radiographic means, since they can be of use both in clinic and in basic research, due to a greater equipment availability and because they allow the analysis of other properties of bone tissue.

Effects of Hydrogen Sulfide and Nitric Oxide on the Permeability of Cultured Trabecular Meshwork Cells

PURPOSE: To investigate the effects of hydrogen sulfide (H₂S) on the permeability of a cultured human trabecular meshwork cells (HTMC) monolayer and its interaction with nitric oxide (NO).METHODS: After exposing primary cultured HTMCs to 0, 50, 100, and 500 µM sodium hydrogen sulfide (NaHS) for 6 hours, the permeabilities through the HTMC monolayer were measured using a Transwell assay with carboxyfluorescein. The production of NO and eNOS mRNA expression were assessed using the Griess assay and reverse transcription-polymerase chain reaction, respectively. In addition, 0, 1, and 10 µM NaHS and 10 µM sodium nitroprusside (SN) were co-exposed to evaluate the possible synergistic effect of H₂S and NO.RESULTS: Greater than 100 µM NaHS increased the permeability through the HTMC monolayer in a dose-dependent manner (p < 0.05). These increased permeabilities were not accompanied by NO production or eNOS mRNA expression (p > 0.05). When 0, 1, and 10 µM NaHS and 10 µM SN were exposed together, there was no significant change of permeability, NO production, or eNOS mRNA expression (all, p > 0.05).CONCLUSIONS: NaHS at high concentrations increased the permeability of the HTMC monolayer, which was not affected by NO. NaHS at low concentrations did not show a synergistic effect with NO. Thus, H₂S at high concentrations may increase trabecular outflow, which may not be associated with NO.

Expression and filtering of TGF-β2 in aqueous humor and trabecular meshwork of Han and Kazakh patients with PACG / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To evaluate the expression level of transforming growth factor β2(TGF-β2)in the aqueous humor and trabecular tissue of patients with primary angle-closure glaucoma(PACG)of Han and Kazakh ethnic groups and the formation of filter bleb after trabeculectomy.<p>METHODS: Prospective research. Between July 2018 to April 2019, 46 PAGG patients(49 eyes)underwent trabeculectomy in our hospital, including 25 Han nationality(26 eyes)and 21 Kazak nationality(23 eyes). Aqueous humor and trabecular tissue were obtained through trabeculectomy. ELISA method was used to detect the content of total aqueous TGF-β2(tTGF-β2)and activated TGF-β2(aTGF-β2). And the expression of TGF-β2 in trabecular tissue was detected by immunohistochemistry and immunofluorescence.<p>RESULTS:Immunohistochemical staining and immunofluorescence staining showed that the expression of TGF-β2 in the trabecular meshwork of Han patients was significantly higher than that of Kazakh patients. ELISA quantitative analysis showed that the aTGF-β2 content of Han and Kazak patients were 172.015±79.367pg/mL and 83.436±41.743pg/mL, respectively, the difference was statistically significant(<i>t</i>=4.794, <i>P</i><0.001). In patients ≥70 years old, the content of tTGF-β2 in the aqueous humor of patients of the two nationalities was 480.124±152.997 and 338.858±72.497pg/mL, respectively, the difference was statistically significant(<i>t</i>=2.421, <i>P</i>=0.026). In the comparison between preoperative and postoperative, there were time differences and interaction effects in intraocular pressure between Han and Kazak patients. At 6mo postoperatively, the formation of type Ⅰ and Ⅱ filter blebs in Han and Kazak patients was different, and the difference was statistically significant(50% <i>vs</i> 78%; χ2=4.841, <i>P</i>=0.028).<p>CONCLUSION: The expression of TGF-β2 in the aqueous humor and trabecular meshwork of patients with PACG in the two ethnic groups is different. The expression of TGF-β2 in the aqueous humor and trabecular meshwork of Kazakh patients is significantly lower, which reduces the promotion of postoperative filtering scar Functional filtration filtration bleb.

A influência do oxido nítrico na fisiopatologia da neuropatia glaucomatosa / The influence of nitric oxide on the pathophysiology of glaucomatous neuropathy

Resumo O oxido nitrico (NO) é um fator relaxante derivado do endotélio e um potente vasodilatador que impacta em vários sistemas em todo o corpo. Estudos comprovam que o fluxo sanguíneo ocular basal é regulado pelo NO, sendo um importante regulador da homeostase, especialmente dentro dos tecidos uveais. A disfunção da produção de NO seria associado ao glaucoma através da alteração da perfusão da cabeça do nervo óptico associado ao aumento da pressão intraocular devido um sistema de drenagem trabecular deficiente. O NO tornou-se uma molécula atraente para o tratamento do glaucoma devido a possibilidade de modulação da drenagem trabecular, abaixando a pressão intraocular e ação neuroprotetora melhorando a perfusão sanguínea na cabeça do nervo óptico.

Abstract Nitric Oxide (NO) is a relaxing endothelium-derived factor and a potent vasodilator that impacts various systems throughout the body. Proven studies of basal ocular blood flow are regulated by NO, being an important regulator of homeostasis, especially within the uveal tissues. The dysfunction of the production associated with glaucoma due to alteration of the optic nerve head associated to the increase of the intraocular pressure by a deficient trabecular meshwork. NO became an attractive molecule for the treatment of glaucoma due to a modulation of the trabecular meshwork, lowering the neuroprotective intra and ocular pressure for a blood surgery in the head of the optic nerve.

Effect of Chronic Benzalkonium Chloride Exposure on Senescence in Trabecular Meshwork Cells

PURPOSE: To determine the possible effects of chronic exposure of low dose benzalkonium chloride (BAK) on trabecular meshwork cells, and to characterize the pathways involved in the effects. METHODS: Trabecular meshwork cells were treated with 0.0005%, 0.00075%, 0.001%, and 0.0025% BAK for 10 minutes; then, the cells were transferred to a new medium for 24 hours. This process was repeated three times. Cell survival was assessed using the MTT assay to determine the non-apoptotic BAK concentration. Senescence-associated (SA)-β-gal staining was performed to compare quantitatively the cellular senescence of BAK-treated cells with the control group. Cells treated with BAK were analyzed by western blot to determine whether the expressions of cell cycle regulators were affected. RESULTS: Two concentrations (0.0005% and 0.00075%) showed persistent cell viability and were chosen for further experiments. After SA-β-gal staining, cells treated with 0.0005% and 0.00075% BAK showed 28% (± 2.08), 37% (± 2.08) increases in cellular senescence expression, respectively, when compared with control cells (p < 0.05). To identify the molecular pathways involved in cell cycle arrest via BAK, western blot analysis was performed on trabecular meshwork cells, resulting in decreased expressions of cyclin E/CDK2, and increased expressions of the upper stream control molecules, p53 and p21. CONCLUSIONS: Chronic exposure to low dose BAK accelerated cell senescence through cell cycle arrest. Because senescent cells of the trabecular meshwork can inhibit its outflow pathway function and ultimately worsen the glaucomatous process, long-term usage of topical glaucoma medications containing BAK should be conducted with caution.

Effect and Mechanism of Phosphodiesterase Inhibitors on Trabecular Outflow

PURPOSE: Phosphodiesterase (PDE) inhibitors increase matrix metalloproteinase (MMP) production by inhibiting re-uptake of adenosine and may potentiate nitric oxide (NO) activity. This study was performed to investigate the effects and mechanisms of PDE inhibitors on trabecular outflow in cultured human trabecular meshwork cells (HTMCs). METHODS: Primary HTMC cultures were exposed to 0, 20, and 50 µM dipyridamole (DPD) or theophylline (TPN). Permeability through the HTMC monolayer was assessed using carboxyfluorescein. The production of NO was assessed using the Griess assay and MMP-2 levels were measured via Western blotting. RESULTS: DPD significantly increased permeability accompanied with increased nitrite concentration and MMP-2 levels (all p 0.05). When treated with DPD and TPN together, both permeability and nitrite production were increased; however, MMP-2 levels showed no difference compared to DPD exposure alone (p > 0.05). CONCLUSIONS: DPD increased trabecular permeability accompanied with increased nitrite production and MMP-2 levels. PDE inhibitors may increase trabecular outflow by increasing MMP-2 levels and by potentiating NO activity through cyclic GMP in HTMC.

The inhibitory effect of FoxF2 shRNA on the expression of extracellular matrix of human trabecular meshwork / 中华实验眼科杂志

Objective To explore the role of forkhead box F2 (FoxF2) in the extracellular matrix of trabecular meshwork.Methods The cultured human trabecular meshwork cells (HTMCs) were divided into Scramble control group and FoxF2 small hairpin RNA (shRNA) group,then FoxF2 shRNA,the FoxF2 restructuring interference carrier was built,HTMCs were infected with FoxF2 shRNA lentivirus.Western blot assay was used to detect the expression of FoxF2 protein and extracellular matrix.Furthermore,Transwell counting experiment was used to analyze the migration ability of HTMCs.Results The cultured HTMCs grew well and showed a long spindle shape.The growth status of HTMCs was well,and their morphological characteristics were consistent with the HTMCs in vivo.The relative expression level of FoxF2 protein in the FoxF2 shRNA group was lower than that in the Scramble control group,with a significant difference between them (0.72 ± 0.02 vs.1.27 ± 0.05;t =16.68,P ＜ 0.01).The relative expression level of fibronectin (FN),collagen type Ⅰ (COL Ⅰ) and α-smooth muscle actin (α-SMA) were 0.43±0.03,0.53 ±0.08 and O.86±0.15 in the FoxF2 shRNA group,and 0.87±0.04,1.66±0.06 and 1.73 ±0.13 in the Scramble control group,respectively,the relative expression levels of FN,COL Ⅰ and α-SMA in the FoxF2 shRNA group were significantly lower than those in the Scramble control group (t =15.08,18.81,7.50,all at P＜0.01).The migration number of HTMCs in the FoxF2 shRNA group was significantly lower than that in the Scramble control group (117.30±11.41 vs.251.00±10.37;t =8.72,P＜0.01).Conclusions The FoxF2 shRNA lentivirus are successfully constructed,which can decrease the expression of FoxF2 in HTMCs.Low expression of FoxF2 can reduce the expression level of extracellular matrix protein in HTMCs and inhibit the migration ability of HTMCs.

Progress of Rho-associated protein kinase inhibitor in the treatment of glaucoma / 国际眼科杂志(Guoji Yanke Zazhi)

@#Glaucoma is a leading cause of irreversible blindness, which is characterized by characteristic optic atrophy and visual field defects. Elevated intraocular pressure(IOP)is a primary risk factor of glaucoma, while the main cause of elevated IOP lies in the increased aqueous outflow resistance in pathological trabecular meshwork(TM), which is the conventional outflow pathway of aqueous humor. Rho-associated protein kinase inhibitor(ROCKi)is the IOP-lowering drug that is directly acting on the TM. The TM cell morphology, cell movement, cytokinesis and cell contraction by alteration of cytoskeleton can be changed by ROCKi to increase aqueous humor outflow facility and decrease IOP. ROCKi is now approved for clinical use in the United States and Japan. Meanwhile, it might play a role in optic nerve protection through increasing retinal vascular perfusion and promoting optic nerve regeneration. In addition, it decreases the possibility of filtration bleb scarring. Therefore, ROCKi has become a new pharmacological option to treat glaucoma. This article reviews the Rho-Rho kinase signaling pathway, the mechanism of ROCKi and its clinical application.

Advances in trabecular meshwork stem cells transplantation for primary open angle glaucoma / 国际眼科杂志(Guoji Yanke Zazhi)

@#Primary open angle glaucoma is a kind of chronic disease characterized by progressive damage to the optic disc as a result of persistent elevation of intraocular pressure. The complicated and unidentified mechanism of primary open angle glaucoma makes its clinical treatment relatively difficult nowadays. In primary open angle glaucoma, IOP elevation is often a result of reduced aqueous humor flow through the trabecular meshwork, which plays an important regulating role in drainage process. The morphology, quantity, structure and function of trabecular meshwork cell can increase the outflow resistance of aqueous humor, leading to elevation of IOP. Research is proving that induced pluripotent stem cells(iPSCs), bone mesenchymal stem cells(BMSCs)and adipose-derived stem cells(ADSCs)have been used for trabecular meshwork cell differentiation and regeneration, providing a reliable cell source for trabecular meshwork stem cell replacement therapy in primary open angle glaucoma. Recent studies have showed that trabecular meshwork stem cells have absolute superiority in differentiating into trabecular meshwork cells, which provides new target for cell transplantation to treat glaucoma. This marks a new era of stem cell therapy for primary open angle glaucoma and also brings new hope to the treatment of glaucoma. This article reviews different types of stem cells for trabecular meshwork transplantation and may provide novel development of therapeutic strategies for primary open angle glaucoma with cell transplantation in the future.

Effect of IL-6 on fibronectin in bovine trabecular meshwork cells cultured <i>in vitro</i> / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To investigate the changes of fibronectin expression in cultured bovine trabecular meshwork cells when cells were stimulated by different concentrations of IL-6 to provide evidence for early diagnosis and new therapy of POAG.<p>METHODS: We identify third-generation bovine trabecular meshwork cells which were got from tissue mass culture method. Then the relative expression of FN gene and protein in cells were detected by Real-Time PCR and Western-blot after 24h stimulation with 0ng/mL, 0.1ng/mL, 0.5ng/mL IL-6.<p>RESULTS: The cultured bovine trabecular cells are coincident with what recorded in the book. Real-time PCR and Western blot showed that the amount of FN mRNA produced by cells was 1.000±0.000, 0.213±0.004, 0.056±0.001, 0.019±0.002 respectively, and the protein expression was 1.167±0.012, 0.662±0.009, 0.238±0.011, 0.061±0.011 respectively. There was a significant difference among four groups(<i>P</i><0.05).<p>CONCLUSION: Cultured bovine trabecular meshwork cells have a negative correlation with the expression of FN protein after being stimulated by exogenous IL-6, and the results are consistent with the actual state of the disease. We speculate that the IL-6 participate in the pathogenesis and progression of POAG by affecting the expression of FN gene and protein and changing the structure of trabecular meshwork.