Research progress of retinal neurovascular unit injury in glaucoma / 国际眼科杂志(Guoji Yanke Zazhi)

Glaucoma is one of the leading causes of vision loss worldwide. More and more studies have suggested that glaucoma is a complicated retinal neurovascular disease. The homeostasis imbalance of retinal neurovascular unit(RNVU)composed of neurons, glial cells and microvascular cells not only induces changes in microvascular structure and glial cells, but also affects the nerve tissue of the retina, resulting in vision loss, which there is no effective treatment to reverse, currently. Exploring the cellular composition and molecular structure of RNVU and investigating the destruction mechanism of normal cellular environment and intercellular connections in glaucoma are of great significance in exploring the pathogenesis and the treatment of glaucoma. The research progress on structural changes and dysfunction of RNVU in glaucoma are reviewed, hoping to provide new ideas for the treatment of glaucoma.

Research progress on genetic model of mouse with glaucoma / 国际眼科杂志(Guoji Yanke Zazhi)

Glaucoma, currently the world's first irreversible blindness, is a complex multifactorial disease with a genetic predisposition, and pathologically elevated intraocular pressure is its risk factor. The pathogenesis of glaucoma is not fully understood, and most existing studies are based on animal models, with mice as the main research object, and the pathological damage process of glaucoma is reconstructed through experimental induction means or transgenic manipulation to further investigate the relevant pathogenesis and pathological changes. The technique of experimentally induced construction of glaucoma mouse models has been studied by many scholars and is gradually becoming mature. And as research in molecular biology and genetics has advanced, more and more studies have focused on the disease genes associated with glaucoma, and transgenic mouse models have become a hot topic in recent years. In contrast to experimental manipulation to control a single factor, gene editing is better able to simulate the complex process of disease pathogenesis. This paper focuses on providing a more complete direction and strategy for model selection in the future research by describing the progress of research on relevant transgenic mouse model of glaucoma.

Research progress of cellular senescence in glaucoma / 中华实验眼科杂志

Cellular senescence is a response process in which cells are activated by ischemia, hypoxia, oxidative stress, DNA damage, reactive oxygen species deposition and other stimulations.Senescent cells markers include such as senescence-associated β-galactosidase (SA-β-gal) activation, P16INK4a upregualtion, senescence-associated heterochromatic foci (SAHF) accumulation, senescence-associated secretory phenotype (SASP) generation, telomere shortening and so on.P16INK4a/Rb and P19 ARF/P53/P21 Cip1 pathways are two classic cell senescence signaling pathways, which are interconnected and independent on each other.In recent years, glaucoma is considered as a blinding eye disease associated with cell senescence.Research on cell senescence in glaucoma mainly focuses on trabecular meshwork and Schlemm cannel endothelial cells senescence leading to increased resistance of aqueous humor outflow pathway, and the mechanism of retinal ganglion cells senescence and treatment in glaucoma.As an irreversible stage before cell death, deeper study on the mechanism of retinal ganglion cells senescence, and specific blocking of cell senescence will provide a new target for reducing the aqueous humor outflow resistance and protecting the optic nerve in glaucoma.This article reviewed characteristics, inducements, molecular signaling pathways of cellular senescence in glaucoma.

Retinal ganglion cell topography and spatial resolving power of eye in the native chicken of Bangladesh / Topografía de células ganglionares de la retina y poder de resolución espacial del ojo en el pollo nativo de Bangladesh

SUMMARY: The distribution of retinal ganglion cells (RGCs) was observed in the retinal wholemount of native chicken (Gallus gallus domestricus) of Bangladesh by using light microscopy. We considered five different anatomic regions (central, nasal, temporal, dorsal, and ventral) of Nissl stained wholemount, and the RGCs were counted, plotted, and measured accordingly. The average area of the retina was 431.75 mm2 while the total number of ganglion cells was 2124431 on average. Only the central area of the retina was the peak density (10400 cells/mm2) area, signifying the acute visual area, whilst the maximum spatial resolving power was 11 cycles/degree. The overall concentration of RGCs gradually declined towards the periphery but the size of cells generally decreased towards centrally. The size of ganglion cell was not uniform (12 to 180 µm2), specifically the central retina, just above the optic disc was packed with tiny-sized cells. The number, topographic distribution, and size of RGCs in native chicken signified their domesticated or terrestrial characters, uneven visual acuteness, and possibly only the central retina was the area for fine vision as the function of RGCs.

RESUMEN: En este studio se observó la distribución de las células ganglionares en la retina (CGR) de pollo nativo (Gallus gallus domesticus) de Bangladesh mediante el uso de microscopía óptica. Consideramos cinco regiones anatómicas diferentes (central, nasal, temporal, dorsal y ventral). Las muestras de CGR se tiñeron con Nissl, posteriormente, se midieron y contó el número de células totales. El área promedio de la retina fue de 431,75 mm2, mientras que el promedio del número total de células ganglionares fue de 2124431. El área central de la retina fue el área de densidad máxima (10400 células / mm2), señalando el área visual aguda, mientras que el poder de resolución espacial máximo fue de 11 ciclos / grado. La concentración general de CGR disminuyó gradualmente hacia la periferia, sin embargo, el tamaño de las células disminuyó hacia el centro. El tamaño de las CGR no fue uniforme (12 a 180 mm2), específicamente en la retina central, por encima del disco óptico, aumentaron significativamente las células pequeñas. El número, la distribución topográfica y el tamaño de las CGR en pollos nativos determinaron las características domésticas o terrestres, agudeza visual desigual y, posiblemente, la función de las CGR, en la retina central era el área de visión fina.

Expression of lncRNA Tsix in a mouse model of N-methyl-D-aspartic acid-induced retinal excitotoxicity and its significance / 中华实验眼科杂志

Objective:To investigate the damage effect of different concentrations of N-methyl-D-aspartic acid (NMDA) to retinal ganglion cells (RGCs) in mice and explore the expression of long noncoding RNA (lncRNA) Tsix in the retina of mice with excitotoxicity as well as the protective effect of lncRNA Tsix on retina and RGCs.Methods:A total of 105 C57B6/J mice at 7-8 weeks of age were selected and randomly divided into the normal control group, 2 mmol/L NMDA group, 10 mmol/L NMDA group, 20 mmol/L NMDA group and 40 mmol/L NMDA group using a random number table method, with 21 mice in each group.In the normal control group, the mice were intravitreally injected with 1 μl of sodium chloride solution in the right eye, and mice were given intravitreal injection of 1 μl of different doses of NMDA according to grouping.At one week after the injection, the thickness of each retinal layer, the number of ganglion cell layer (GCL) cells and the number of RGCs were analysed and compared among different groups through optical coherence tomography (OCT), hematoxylin-eosin staining, retinal whole mount staining and immunofluorescence staining.RNAscope in situ hybridization was used to verify the expression of lncRNA Tsix in the GCL of different groups.The quantitative real-time PCR was used to detect the transcript levels of Tsix in different groups.This study was approved by an Ethics Committee of Tianjin Medical University (No.SYXK2018-0004), and the use of experimental animals was in accordance with the regulations of Tianjin Medical University and ARVO statement. Results:The OCT results showed that the total retinal thickness of mice in the 2, 10, 20 and 40 mmol/L NMDA groups were (255.00±6.63), (252.40±6.41), (248.67±6.20) and (229.11±10.37)μm, respectively, which were thinner than (269.60±20.01)μm in the normal control group, and the differences were statistically significant (all at P<0.05). Hematoxylin-eosin staining showed that the cells in the GCL of the normal control group were uniform and compact, and arranged in a single layer with large and round nuclei.In the NMDA groups, the cells were uneven in volume with vacuoles and nuclear pyknosis.The cell density in the GCL was decreased significantly with the increasing NMDA doses in NMDA groups in comparison with the normal control group, and the differences were statistically significant (all at P<0.05). In the 20 mmol/L NMDA group, the cell density in the GCL was reduced to half of the normal control group.The results of retinal whole mount staining showed that the density of β3-tubulin-positive RGCs was decreased significantly as the dose of NMDA increased in NMDA groups, and the differences were statistically significant compared with the normal control group (all at P<0.05). The number of RGCs in the 10 mmol/L NMDA group was reduced to half of that in the normal control group.RNAscope results showed that lncRNA Tsix was mainly expressed in the cytoplasm of the GCL cells.The proportion of lncRNA Tsix-positive cells was significantly reduced with the increase of the NMDA dose ( F=13.670, P<0.01). The quantitative real-time PCR results verified that the trend of Tsix expression was consistent with the RNAscope result. Conclusions:NMDA exerts a dose-dependent damage to the layer thickness of mouse retina and RGCs.The expression of lncRNA Tsix in mouse retina is mainly enriched in the cytoplasm of the cells in the GCL, and the transcript level of Tsix is reduced with the increase of NMDA concentration and have a protective effect on RGCs.

Comparison of OCT findings of schizophrenia patients using FGA, Clozapine, and SGA other than Clozapine

ABSTRACT Objective: The effect of antipsychotic (AP) drugs on optical coherence tomography (OCT) findings in schizophrenia has not yet been fully elucidated. In this study, we aimed to investigate the effects of APs (the first generation antipsychotic group [FGAG], the second generation antipsychotic group [SGAG], the clozapine group [CG]) on OCT findings in schizophrenia. Methods: The thickness of the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), and choroidal thickness were measured using a spectral OCT device. Results: No significant difference was found between FGAG, SGAG, CG (p > 0.05) while there was a significant difference between the control group and the patients group in terms of RNFL, GCL, and IPL (p < 0.05). A significant difference between SGAG and CG, FGAG (p < 0.05); between control group and FGAG (p < 0.05) were found in terms of choroidal thickness. Conclusion: These findings suggested the deterioration of the metabolic parameters due to the SGA use. Thinner choroidal layer thickness in the CG compared to the SGAG and control group was thought to be related to the patients using clozapine had a resistance to the treatment.

Optical coherence tomography detection of changes in inner retinal and choroidal thicknesses in patients with early retinitis pigmentosa / Detecção por tomografia de coerência óptica das alterações da retina interna e da espessura de coroide em pacientes com retinite pigmentosa precoce

ABSTRACT Purpose: To evaluate the inner retinal and choroidal thicknesses in patients with early retinitis pigmentosa. Methods: We analyzed spectral-domain optical coherence tomography images of 35 retinitis pigmentosa patients and 40 healthy individuals. We measured macular and ganglion cell complex thicknesses. We took choroidal thickness measurements in the subfoveal region and 500, 1,000, and 1,500 mm from the foveal center. Results: Patients with retinitis pigmentosa had significantly thinner macular thicknesses and choroidal thicknesses in all measurements, and their individual ganglion cell complex thickness measurements were lower than those in healthy individuals. The mean ganglion cell complex thickness was significantly lower in patients with retinitis pigmentosa than that in controls. The mean macular thickness was significantly correlated with the mean choroidal and mean ganglion cell complex thicknesses. (We found no correlation between the mean choroidal thickness and the mean ganglion cell complex thickness). Conclusions: The choroid was mildly affected in our patients with early retinitis pigmentosa. The tendency toward significance in the inner retina was possibly caused by a good visual acuity.

RESUMO Objetivo: Avaliar as espessuras internas da retina e da coroide em pacientes com retinite pigmentosa precoce. Métodos: Foram analisadas imagens de tomografia de coerência óptica de domínio espectral de 35 pacientes com retinite pigmentosa e 40 indivíduos saudáveis. Medimos a espessura do complexo de células maculares e ganglionares. Realizamos medições da espessura da coroide na região subfoveal e a 500 mm, 1000 mm e 1500 mm do centro da fóvea. Resultados: Pacientes com retinite pigmentosa apresentaram espessuras maculares e da coroide significativamente mais finas em todas as medições e suas medidas individuais da espessura do complexo de células ganglionares foram inferiores às de indivíduos saudáveis. A espessura média do complexo de células ganglionares foi significativamente menor nos pacientes com retinite pigmentosa do que nos controles. A espessura macular média foi significativamente correlacionada com as espessuras médias do complexo das células de coroide e das células ganglionares médias. Não encontramos correlação entre a espessura media da coroide e a espessura media do complexo de células ganglionares. Conclusões: A coroide foi levemente afetada em nossos pacientes com retinite pigmentosa precoce. A tendência à significância na retina interna foi possivelmente causada por uma boa acuidade visual.

Retinal Ganglion Cell Layer Thicknesses and Visual Functions in Patients with Bilateral Temporal Optic Atrophy

PURPOSE: To investigate correlations between macular retinal ganglion cell (RGC) layer thickness and best-corrected visual acuity (BCVA) and visual field parameters in patients with bilateral temporal optic atrophy.METHODS: Thirty eyes of 15 patients with bilateral temporal optic atrophy and 30 eyes of 15 normal subjects that were age- and sex-matched were included in the study. We measured the thicknesses of the RGC layers of posterior poles using optical coherence tomography volume scanning. The RGC layer was divided into nine zones based on the Early Treatment of Diabetic Retinopathy Study baseline. Possible correlations of the RGC layer with the BCVA and visual field parameters were determined.RESULTS: The RGC layer thickness was significantly thinner in all patients compared to those in the control group (p = 0.001). The RGC layer thicknesses in the inner superior, inner temporal, inner inferior, and inner nasal areas were significantly correlated with the BCVA (r = −0.650, r = −0.626, r = −0.616, and r = −0.636, respectively; p = 0.000). The RGC layer thicknesses in the outer superior, outer temporal, outer inferior, and outer nasal areas were significantly correlated with the mean deviation of the visual field test (r = 0.470, r = 0.349, r = 0.496, and r = 0.469, respectively; p < 0.05).CONCLUSIONS: In patients with bilateral temporal optic atrophy, the RGC layer thickness in the medial region was correlated with the BCVA, and the RGC layer thickness in the lateral region was correlated with the mean deviation of the visual field test.

Comparison of Retinal Ganglion Cell Damage in Glaucoma and Retinal Vein Occlusion by Visual Field

PURPOSE: We analyzed and compared retinal ganglion cell damage between patients with glaucoma and those with branched retinal vein occlusion (BRVO). We performed two types of visual field examinations. METHODS: We retrospectively reviewed the medical records of 40 glaucoma eyes and 40 BRVO eyes. We compared the median deviation (MD), the pattern standard deviation (PSD), and sensitivity of damaged visual hemifield from frequency-doubling technology (FDT) C24-2 and standard automated perimetry (SAP) C24-2 visual field tests evaluation. We sought correlations between the MDs and retinal nerve fiber layer thickness as revealed by optical coherence tomography. RESULTS: MDs did not differ between the groups. PSD value was higher in glaucoma patients with FDT C24-2 test (p = 0.022), but no difference between two groups with SAP C24-2 test (p = 0.144). In terms of the sensitivity of the damaged visual hemifield, glaucoma patients had larger areas of damage in the FDT C24-2 test (p < 0.01). In regression analyses, the log R2 values of both tests were higher in glaucoma patients. CONCLUSIONS: Glaucoma patients had a greater damaged visual field area in the FDT C24-2 test than the SAP C24-2 test. The BRVO patients exhibited similar extents of damage in both tests. Thus, the subtypes and distributions of damaged retinal ganglion cells may differ between the conditions, facilitating differential diagnosis.

Rac1 Modulates Excitatory Synaptic Transmission in Mouse Retinal Ganglion Cells / 神经科学通报·英文版

Ras-related C3 botulinum toxin substrate 1 (Rac1), a member of the Rho GTPase family which plays important roles in dendritic spine morphology and plasticity, is a key regulator of cytoskeletal reorganization in dendrites and spines. Here, we investigated whether and how Rac1 modulates synaptic transmission in mouse retinal ganglion cells (RGCs) using selective conditional knockout of Rac1 (Rac1-cKO). Rac1-cKO significantly reduced the frequency of AMPA receptor-mediated miniature excitatory postsynaptic currents, while glycine/GABA receptor-mediated miniature inhibitory postsynaptic currents were not affected. Although the total GluA1 protein level was increased in Rac1-cKO mice, its expression in the membrane component was unchanged. Rac1-cKO did not affect spine-like branch density in single dendrites, but significantly reduced the dendritic complexity, which resulted in a decrease in the total number of dendritic spine-like branches. These results suggest that Rac1 selectively affects excitatory synaptic transmission in RGCs by modulating dendritic complexity.

The time relationship of retinal light threshold fluctuations and retinal nerve fiber layer and ganglion cell complex thickness changes on high-risk primary open-angle glaucoma / 中华眼底病杂志

Objective To investigate the time relationship of the change,and diagnostic accuracy and sensitivity between retinal light threshold fluctuations (LTF) and retinal nerve fiber layer (RNFL) and ganglion cell complex(GCC) thickness on high-risk primary open-angle glaucoma (POAG).Methods Totally 319 patients (319 eyes) with high-risk in POAG from the First Affiliated Hospital of Kunming Medical Universityand during December 2009 and December 2017,50 healthy individuals (50 eyes) as control were collected in this longitudinal cohort study.Visual field and OCT were reviewed every 6 months on the high-risk group and every 12 months on the control group.High-risk groups inclusion criteria:vertical C/D≥0.6;early visual field defect (according to glaucoma visual field damage GSS2 quantitative grading standards,mean deviation and pattern standard deviation of central field exceeds the border as an early visual field defect);continuous repeatable results.The first field and OCT results in the absence of visual field defects and C/D≥0.6,which were conformed reliability indicators and removed learning effects as a baseline.When patients achieve POAG diagnosis criteria first time which was recorded as a turning point.And they were divided into early group meanwhile were ended of follow-up.After the last follow-up,the inspection data was segmented counted in yearly interval.The changes of LTF,thickness of RNFL and GCC during the follow-up period in the early POAG group and the control group were observed.The loss rate and change rate in each period were compared for the assessment of their trends with time.Followed by calculation of the area under receiver operating curves (AUC) to compare the predicted value of POAG and the sensitivity at 95％ specificity in each period.Results After last follow-up,totally 67 patients 67 eyes (early POAG group,37 males and 30 females) were entered the turning point.The mean follow-up of the early POAG group and the control group were 6.6 and 6.4 years.The average RNFL thickness was 79.05± 8.09 μm,GCC thickness was 71.58 ± 8.41 μm,LTF was -6.05 ± 7.02 dB in early POAG group.The average RNFL thickness was 93.49± 6.24 μrm,GCC thickness was 79.72± 6.32 μm,LTF was-0.31 ± 0.58 dB in the control group.The differences of LTF and the thickness of RNFL and GCC were statistically significant (t=-5.97,-10.42,-5.60;P＜0.001).The AUC of RNFL,GCC thickness and LTF increased with time in the early POAG group.The sensitivity was gradually increased at 95％ specificity:5th year before to at turning point,RNFL thickness AUC was 0.15,0.65,0.71,0.77,0.85,0.92,and sensitivity was 20％,56％,61％,65％,70％,76％,respectively;GCC thickness AUC was 0.12,0.53,0.69,0.74,0.82,0.90,and sensitivity was 14％,53％,69％,74％,82％,90％,respectively;the AUC of LTF was 0.10,0.21,0.33,0.75,0.86,0.91,and sensitivity was 7％,17％,44％,65％,78％,87％,respectively.Conclusions The earliest time of structural functional damage of POAG is at the 4th year before confirmed,simultaneous RNFL diagnosis accuracy and sensitivity are better than GCC and LTF.The earliest time of visual functional damage of POAG is at the 2th year before confirmed,simultaneous LTF diagnosis accuracy and sensitivity are better than RNFL and GCC.

Retinal Nerve Fiber Layer and Macular Retinal Ganglion Cell Layer Thicknesses in Healthy Korean Children

PURPOSE: To measure the thicknesses of the circumpapillary retinal nerve fiber layer (RNFL) and macular retinal ganglion cell-inner plexiform layer (GCIPL) by optical coherence tomography (OCT) in healthy Korean children and adolescents. METHODS: Circumpapillary RNFL and macular GCIPL thicknesses were measured by OCT in 352 healthy eyes of 352 children and adolescents (child-adolescent group) aged 5–17 years and in 159 healthy eyes of 159 adults (adult group) aged 18-75 years. The difference in RNFL and GCIPL thicknesses between the groups and the effects of age and refractive errors on the measurements were evaluated. RESULTS: The mean age of the children and adults were 9.7 ± 3.6 and 44.7 ± 15.7 years, respectively. The mean of the average RNFL and GCIPL thicknesses were 103.1 ± 9.2 and 85.7 ± 4.6 µm, respectively, in the children group and 97.8 ± 8.2 and 82.9 ± 4.4 µm, respectively, in the adult group. The child-adolescent group had greater RNFL and GCIPL thicknesses compared to the adult group in all areas (p < 0.05) with the exception of the RNFL thickness in the temporal quadrant (p = 0.555). A thinner RNFL and thinner GCIPL were significantly associated with older age and greater myopia (p < 0.001). CONCLUSIONS: The mean RNFL and GCIPL thicknesses measured by OCT in the healthy eyes of children and adolescents were 103.1 and 85.7 µm, respectively. Children and adolescents had a thicker RNFL and GCIPL compared to adults.

The reaction pattern rules of mouse retinal ganglion cell under different wavelengths of light stimulation / 中华实验眼科杂志

Objective To explore the reaction pattern rules of mouse retinal ganglion cells potential under different wavelengths of light stimulation.Methods Thirty SPF grade 3-week-old C57BL/6 mice were used for ex vivo whole mount retina preparation.The cells firing activities were recorded on patch clamp system with on cell touch mode under stimulation of 400 nm,580 nm and white light,respectively.According to different reactions to different light stimulation,the cells were classified into 400 nm sensitive RGC,580 nm sensitive RGC and color vision insensitive RGC.Then the cells were further classified according to light ON type,light ON/OFF type or light OFF type.The RGC's baseline firing pattern (baseline firing frequency,burst firing frequency) and light activation firing pattern (response pattern,light response firing frequency,light response firing amplification) were compared among different RGC classifications.Results Eighty-two RGCs were recorded in total.The frequency of spontaneous firing activity ranged from 0.00 Hz to 32.33 Hz among different RGCs.400 nm sensitive RGCs were 52 (63.41％),580 nm sensitive RGCs were 29(35.37％) and color vision insensitive RGC was 1 (1.22％).OFF type RGC was the main cell type in 400 nm sensitive group (36.29％),and ON/OFF type RGC was the main cell type in 580 nm sensitive group (34.48％).The firing amplification in 580 nm sensitive RGC was (22.93±10.23) Hz,which was significantly higher than (14.44± 10.11) Hz in 400 nm sensitive RGC (t =4.060,P =0.044).The firing amplification in 580 nm sensitive ON type RGC was (24.17±8.98)Hz,which was significantly higher than (11.12±10.35)Hz in 400 nm sensitive ON type RGC (t =5.373,P =0.021).Conclusions There is no specific firing pattern rules among different light sensitive RGCs.In the future,artificial color vision may be achieved through personalized electric stimulation and learning feedback strategy.

Advances in research on calcium channel inhibition mediating axonal stabilization for repair of optic nerve injury / 国际眼科杂志(Guoji Yanke Zazhi)

@#Optic nerve injury is a common nervous system disease. Its basic pathological features are axonal degeneration and apoptosis of retinal ganglion cells(RGCs), which causes numbers of symptoms including visual dysfunction. Axonal degeneration, including axonal selective degradation, Wallerian degeneration induced by axonal transection, and apoptosis-induced axonal degeneration(axonal apoptosis), is an important part of neurodevelopment, axonal remodeling, and injury response process. Axonal degeneration is one of the initial steps in many traumatic neurological disorders, and damaged axons are generally unable to regenerate, which leads to neuronal cell apoptosis. Neuronal apoptosis causing the degeneration of both cell bodies and axons commonly occurs during the development of brain, as a result of various neuronal damages. Studies in recent years have confirmed that calcium is the main regulator of axonal degeneration. When an optic nerve crush(ONC)occurs, the degree of acute axonal degeneration(AAD)can be reduced by using calcium channel inhibitors to prevent the influx of calcium ions into axons, which will also improve the survival rate of RGCs and accelerate the regeneration of axons.

Functional Analysis and Immunochemical Analyses of Ca²⁺ Homeostasis-Related Proteins Expression of Glaucoma-Induced Retinal Degeneration in Rats

The retinal degeneration resulting from elevated intraocular pressure was evaluated through functional and morphological analyses, for better understanding of the pathophysiology of glaucoma. Ocular hypertension was induced via unilateral episcleral venous cauterization in rats. Experimental time was set at 1 and 3 days, and 1, 2, 4, and 8 weeks post-operation. Retinal function was analyzed using electroretinography. For morphological analysis, retinal tissues were processed for immunochemistry by using antibodies against the calcium-sensing receptor and calcium-binding proteins. Apoptosis was analyzed using the TUNEL method and electron microscopy. Amplitudes of a- and b-wave in scotopic and photopic responses were found to be reduced in all glaucomatous retinas. Photopic negative response for ganglion cell function significantly reduced from 1-day and more significantly reduced in 2-week glaucoma. Calcium-sensing receptor immunoreactivity in ganglion cells remarkably reduced at 8 weeks; conversely, protein amounts increased significantly. Calcium-binding proteins immunoreactivity in amacrine cells clearly reduced at 8 weeks, despite of uneven changes in protein amounts. Apoptosis appeared in both photoreceptors and ganglion cells in 8-week glaucomatous retina. Apoptotic feature of photoreceptors was typical, whereas that of ganglion cells was necrotic in nature. These findings suggest that elevated intraocular pressure affects the sensitivity of photoreceptors and retinal ganglion cells, and leads to apoptotic death. The calcium-sensing receptor may be a useful detector for alteration of extracellular calcium levels surrounding the ganglion cells.

Progress in the detection of macular ganglion cell complex thickness / 第二军医大学学报

Retinal ganglion cells are closely related to visual function. Retinal ganglion cell apoptosis and axonal injury can be found in many blinding eye diseases, such as primary glaucoma, optic neuritis, diabetic retinopathy, and atrophic age-related macular degeneration. Ganglion cells mainly exist in the retinal nerve fiber layer, the ganglion cell layer and the inner plexiform layer of the macular area. These three structures are collectively referred to as the retinal ganglion cell complex, and change of the thickness reflects the state of the retinal ganglion cell. It has been reported that ganglion cell complex thickness is thinner in the injured retinal ganglion cells. Therefore it is important to detected thickness of retinal ganglion cell complex in the diagnosis of ocular disease and the evaluation of its severity and prognosis. In this paper, we reviewed the recent progress in the detection of retinal ganglion cell complex thickness in various eye diseases to assist the early diagnosis, treatment and evaluating prognosis of associated ophthalmopathy.

The visual basis of the biological clock "sees" the light:intrinsically photosensitive retinal ganglion cells / 中华实验眼科杂志

Mammalian eyes mediate both image-forming and non-image-forming visual functions. Non-image-forming vision provides a measure of the ambient light for the purposes of synchronization of circadian clocks to light/dark cycles and regulation of pupil size,pineal melatonin production and other functions. Traditionally,people used to believe that the classical photoreceptors (rods and cones) regulate both image-forming and non-image-forming visual pathways. However,a small subset of retinal ganglion cells called intrinsically photosensitive RGCs ( ipRGCs) has been identified to be a third type of mammalian photoreceptor and determined to be photosensitive, recently. The discovery of ipRGCs has allowed for rapid progress in the past decade toward understanding the non-image-forming visual system,especially about how the circadian clock complete the synchronization with the light/dark cycle. The anatomical and developmental characteristics of ipRGCs, as well as its biological functions and regulation were reviewed in this paper.

Research progress of measurement of retinal ganglion cell complex using optical coherence tomography in glaucoma / 中华实验眼科杂志

Glaucoma mainly affects the axon and cell body of retinal ganglion cells (RGCs).Optical coherence tomography (OCT) is a kind of imaging machine with noncontact,high scanning speed and high resolution,can be used for quantitative measurement of retinal ganglion cell complex (GCC) thickness or ganglion cell-inner layer (GCIPL) thickness.GCC includes nerve fiber layer,ganglion cell layer and inner cluster layer,GCIPL only includes ganglion cell layer and inner cluster layer time domain OCT (TD-OCT) can only measure the total thickness of the macular region,in fact,some levels are not involved in the progress of glaucoma,which leads to a decrease in specificity and sensitivity.At present,spectral domain OCT (SD-OCT) is used for measuring GCC and GCIPL.It gains faster scanning speed than traditional TD-OCT,and can scan more locations and form 3D images in macular region.Therefore,it is helpful to improve the sensitivity and specificity of detecting the damage of glaucoma by refining the stratification of the macular retina and making the qualitative measurement of the inner layer of retina.Three scanning modes and methods are commonly used,RTVue-100 OCT,Cirrus HD-OCT,3D OCT,and the three methods have their own advantages.Measurement of the thickness of GCC by OCT may be influenced by factors such as age,sex,axial length,race and signal intensity.In recent years,many studies have indicated that GCC or GCIPL has a good consistency with the visual field,and can be used in early diagnose and regular follow-up of glaucoma.The future research should be devoted to normal database establishment of GCC and GCIPL thickness parameters with different age and different ethnic and clinical trials and follow-up study should be performed to explore the change rules of those paremeters.

Retinal ganglion cell-conditioned medium alters the differentiation of rat retinal progenitor cells / 眼科新进展

Objective To investigate the effects of retinal ganglion cell-conditioned medium on the differentiation of retinal stem cells.Methods Rettial stem cells and retinal ganglion cells were isolated from rats,and immunofluorescence staining was applied to identify rat retinal stem cells and retinal ganglion cells with Nestin and Thy-1 antibody,respectively.Retinal stem cells were cultured in presence or absence of retinal ganglion cell-conditioned medium for 72 h,followed by detection of Nestin,PAX6,Thy-1 and Bin-3 gene expression in retinal stem cells by qPCR.Results isolated retinal stem cells were Nestin positive,and retinal ganglion cells were Thy-1 positive,indicating the success of isolation.Compared to retinal stem cells cultured without ganglion cellconditioned medium,ones cultured with ganglion-conditioned medium had significantly downregulated expression of Nestin and PAX6 (both P ＜ 0.000 1),and markedly upregulated expression of Thy-1 and Brn-3 (both P ＜ 0.05).Conclusion Retinal ganglion cell-conditioned medium can induce the differentiation of retinal progenitor cells into retinal ganglion-like cells.

Study of the neuroprotective effects and mechanisms of Tianma Gouteng Decoction on retinal ganglion cells in rat optic nerve crush model / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To observe the mechanism of Tianma Gouteng Decoction on the protein molecular level in the optic nerve crush model rats.METHODS:Totally 36 participants 36 male Wistar rats were divided randomly into six groups(6 in every group):normal control group,negative control group,Tianma Gouteng Decoction treatment groups (con-centrations were 0.6g/mL,1.2g/mL,2.4g/mL respictively) and ginkgo biloba tablets positive control group (concentrations was 1.2mg/mL).Nothing was done in the normal control group.The optic nerve of right eye in the other groups was done with the optic nerve crush model.Normal control group and negative control group was treated only with water.The average grey scale values of the N-methyl-D-aspartic acid receptor 2B (NMDA2B) receptor protein,beta-amyloid protein (Aβ) in the average grey scale values were detected.RESULTS:The average grey scale value of Tianma Gouteng Decoction in low,medium and high dose groups about NMDA2B receptor protein was significantly less than that of the negative control group (all P＜0.001),and there was no significant difference with the positive control group (P=0.092,0.411,0.676),the difference between normal control group and negative control group was significant (P＜0.001).The high dose group of betaamyloid's average grey scale value reduced significantly than the negative control group (P=0.030,0.001).The low dose group than the negative control group was not obviously (P=0.614).The high dose group was not significantly different from the positive control group (P=0.927),the difference between normal control group and negative control group was significant (P＜0.001).CONCLUSION:Tianma Gouteng Decoction can go through the decrease of the NMDA2B receptor protein expression and the control of beta-amyloid deposition to reduce the retinal ganglion cell injury and apoptosis.