Search

This study aimed to develop and evaluate a guinea pig model for glaucoma, comparing resultant eyeball enlargement with an existing myopia model. Thirty guinea pigs underwent intracameral injection of magnetic microspheres to induce chronic ocular hypertension (COH). Intraocular pressure (IOP) was systematically monitored, revealing a successful induction of COH in 73.33% of the guinea pigs. The mean IOP increased from a baseline of 18.04 ± 1.33 mmHg, reaching a peak at week 3 (36.31 ± 6.13 mmHg) and remaining elevated for at least 7 weeks. All data are presented as mean ± standard deviation of the mean. Subsequently, detailed assessments were conducted to validate the established glaucoma model. Immunofluorescent staining demonstrated a significant decrease in the density of retinal ganglion cells (RGC) in the glaucoma group. Optic disc excavation and notable thinning of the lamina cribrosa (LC) were observed. The quantity of optic nerve ax·ons in glaucoma group gradually decreased from baseline (44553 ± 3608/mm 2 ) to week 4 (28687 ± 2071/mm 2 ) and week 8 (17977 ± 3697/mm 2 ). Moreover, regarding the global enlargement of eyeballs, both the transverse and longitudinal axis in glaucomatous eyes were found to be significantly larger than that in myopic eyes, particularly in the anterior chamber depth (1.758 ± 0.113 mm vs. 1.151 ± 0.046 mm). These findings indicate distinct patterns of structural changes associated with glaucoma and myopia in the guinea pig model. This guinea pig model holds promise for future research aimed at exploring biomechanical mechanisms, therapeutic interventions, and advancing our understanding of the relationship between glaucoma and myopia., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: This study aims to investigate the impact of axial elongation on ganglion cell complex thickness (GCCT) and retinal capillary density (CD) using wide-field swept-source optical coherence tomography angiography., Methods: A retrospective cross-sectional analysis was conducted involving 506 eyes. Fovea-centered scans were obtained to assess the subregional GCCT and capillary density across the whole retina, the superficial capillary plexus (SCP), and deep capillary plexus (DCP) among three groups: normal control, high myopia (HM) eyes with axial length < 28 mm, and HM eyes with axial length > 28 mm. Regional variations (central vs. peripheral, quadrants difference [superior, inferior, nasal, and temporal]) were analyzed., Results: In HM eyes with axial length > 28 mm, GCCT and retinal CD exhibit a general decline in most regions (P < 0.05). In HM eyes with axial length < 28 mm, significant reductions were observed specifically in peripheral regions, as in the GCCT beyond the 3 × 3 mm2 area and CD in the 9-12 mm whole retina, 9-12 mm superior SCP, and 6-12 mm DCP (P < 0.05). Maximum GCCT and retinal CD reduction with axial elongation was observed in subregions beyond 6 × 6  mm2., Conclusions: GCCT beyond the 3 × 3 mm2 area and peripheral retinal CD beyond the 6 × 6  mm2 area were more susceptible to axial elongation and are thereby deserving of particular attention., Translational Relevance: It is necessary to evaluate different regions during the clinical assessment of the effect of myopia on the fundus and pay close attention to the peripheral retina.

Glaucoma is a common neurodegenerative disease and a leading cause of irreversible blindness worldwide. Retinal microglia-mediated neuroinflammation is involved in the process of optic nerve damage, but the mechanisms driving this microglial activation remain mostly elusive. Previous investigations reported that microRNAs are associated with the retinal microglial reaction and neural apoptosis. In the present study, we found that microRNA-93-5p (miR-93) played a key role in the reaction of retinal microglial cells in vivo and in vitro. The miR-93 level was significantly reduced in the retinae of rat acute ocular hypertension (AOH) models, which were accompanied by retinal microglial activation, overproduction of inflammatory cytokines, and subsequent retinal ganglion cells (RGCs) death, versus the retinae of controls. The induction of miR-93 overexpression significantly reduced microglial proliferation, migration and cytokine release, inhibited the expression of the target gene signal transducer and activator of transcription 3 (STAT3) and p-STAT3, and was associated with a reduced loss of RGCs. Treatment with a STAT3 inhibitor also decreased retinal microglial activation after AOH injury. Taken together, these results suggest that the miR-93/STAT3 pathway is directly related to the downregulation of retinal microglia-mediated neuro-inflammation and showed a neuroprotective effect. Regulating microglial activation through miR-93 may serve as a target for neuroprotective therapy in pathological ocular hypertension.

Background: Neuromyelitis optica spectrum disorder-optic neuritis (NMOSD-ON) can now be distinguished from other types of ON as a specific disease by the Aquaporin-4 antibody (AQP4-Ab) test. NMOSD-ON can cause severe retinal nerve fiber layer (RNFL) damage. The optical coherence tomography (OCT) characteristics between NMOSD- ON and idiopathic optic neuritis (IDON) were seldom studied in Asians., Methods: This prospective case-control study involved 152 eyes from 143 optic neuritis (ON) patients. All the patients were divided into either the NMOSD-ON group or the IDON group based on the AQP4-Ab test. The retinal nerve fiber layer thickness (RNFLT), retinal thickness (RT), and choroidal thickness (CT) were measured by spectral-domain OCT and compared to the 60 age- and gender-matched healthy controls. The association between RNFLT and best corrected visual acuity (BCVA) was examined., Results: The RNFLT was significantly thinner in all ON patients than in healthy controls, while NMOSD-ON eyes were significantly more affected than IDON eyes in all quadrants (p < 0.01). NMOSD-ON patients had stronger visual function impairment than IDON patients (p < 0.01). RNFLT was related to BCVA in both the NMOSD-ON and IDON groups. Microcystic macular edema (MME) was identified in 28 patients (19.58%) and in 29 of 152 eyes (19.08%), including 20 of 40 eyes (50%) previously affected by ON. MME was more common in patients with NMOSD-ON (32.2%) than in those with IDON (10.75%) (p = 0.001)., Conclusions: The NMOSD-ON group had more pronounced RNFLT thinning and visual function impairment than the IDON group. MME prevalence was higher in NMOSD-ON and was associated with higher frequency of clinical relapses.

Purpose: To analyse miRNA regulation in a rat model of acute ocular hypertension (AOH)., Methods: Acute ocular hypertension (AOH) was induced in the left eye of adult albino rats by inserting a cannula connected with a saline container into the anterior chamber. The contralateral eye served as a control. Seven days later, animals were killed. Retinas were used either for quantitative analysis of retinal ganglion cells (RGCs) and microglial cells or for miRNA array hybridization, qRT-PCR and Western blotting., Results: Anatomically, AOH caused axonal degeneration, a significant loss of RGCs and a significant increase in microglial cells in the ganglion cell layer. The miRNAs microarray analysis revealed 31 differentially expressed miRNAs in the AOH versus control group, and the regulation of 12 selected microRNAs was further confirmed by qRT-PCR. Bioinformatic analysis indicates that several signalling pathways are putatively regulated by the validated miRNAs. Of particular interest was the inflammatory pathway signalled by mitogen-activated protein kinases (MAPKs). In agreement with the in silico analysis, p38 MAP kinase, tumour necrosis factor-alpha (TNF-α) and iNOS proteins were significantly upregulated in the AOH retinas., Conclusions: Acute IOP elevation led to changes in the expression of miRNAs, whose target genes were associated with the regulation of microglia-mediated neuroinflammation or neural apoptosis. Addressing miRNAs in the process of retinal ischaemia and optic nerve damage in association with high IOP elevation may open new avenues in preventing retinal ganglion cell apoptosis and may serve as target for future therapeutic regimen in acute ocular hypertension and retinal ischaemic conditions., (© 2016 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: To evaluate the effect of intravitreal triamcinolone acetonide (TA) on the activation of retinal microglia cells (RMGCs) and survival of retinal ganglion cells (RGCs) in an optic nerve crush (ONC) model., Methods: Adult female Sprague-Dawley rats underwent a standardized ONC and either received an intravitreal injection of TA (TA group) or of phosphate-buffered saline (PBS, PBS group) in the right eyes. At 1, 3, 7, 14 and 28 days after the ONC, the animals were killed. The retinas were examined by immunohistochemistry, light microscopy, Western blot or retrograde labelling of RGCs by fluorogold injected into the superior colliculi., Results: The TA group as compared to the PBS control group showed a significantly (p < 0.0001) lower density of activated RMGCs, at 14 days [4.2 ± 1.6 versus 9.3 ± 2.2 cells/high-power microscopic field (HPF)] and at 28 days (2.3 ± 1.1 versus 4.4 ± 1.5 cells/HPF), and with a significantly lower expression of inflammatory factors. Central density of RGCs as stained by haematoxylin-eosin or by fluorogold was significantly (all p < 0.05) more reduced in the PBS group than in the TA group at days 14 and 28 after baseline. The survival rate (cell density in the study eye as compared to cell density in the contralateral unaffected eye) was significantly higher in the TA group than in the PBS group on days 14 (58% versus 45%; p = 0.003) and 28 (52% versus 41%; p = 0.022)., Conclusions: Intravitreal TA as compared to intravitreal PBS was associated with a lower density of activated RMGCs and a higher density of surviving RGCs in an ONC model., (© 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: To report the thickness of the retina, retinal ganglion cell (RGC)-related layers, and choroid in healthy subjects using swept source optical coherence tomography (SS-OCT)., Methods: One hundred and forty-six healthy volunteers were consecutively recruited for this prospective observational study. Thickness of retina, RGC-related layers, and choroid in the standard early treatment of diabetic retinopathy study (ETDRS) grid were automatically measured using one SS-OCT (DRI OCT-1, Topcon, Japan). The IOL Master (Carl Zeiss Meditec, Germany) was used to measure axial length (AL)., Results: Thicknesses of the average macular ganglion cell complex (GCC) and ganglion cell-inner plexiform layer (GCIPL) were 105.3±9.7 and 78.5±6.2 um respectively. Neither of them was significantly related with sex, age, or AL. Both showed strong correlations with retinal thickness (r=0.793, p=0.000; r=0.813, p=0.000, respectively) and with similar topographic distributions within the retina. The thicknesses of retina and GCC/GCIPL in the inner sectors were significantly higher than in the outer sectors of the EDTRS area, while in the same region of the macula, the choroid exhibited completely different patterns of topographic variation. Men had 7.8 um thicker retina and 34.9 um thicker choroid than women after adjustment for age and AL (all p<0.05). Age and AL could significantly influence the choroidal thickness but not the retina (all p<0.05)., Conclusion: Thickness of GCC/GCIPL in healthy Chinese individuals is not dramatically different across gender, age, and AL groups in terms of ETDRS grid, but sex is critical for retinal and choroidal thickness. Choroidal structure (but not retinal) can be significantly influenced by age and AL.

Objective: To investigate the changes of retinal oxygen saturation (Sat O2) concentrations, choroidal thickness (CT), and retinal nerve fibre layer (RNFL) in eyes with trabeculectomy-required acute primary angle closure (APAC)., Design: Prospective, longitudinal study., Participants: Twenty-three eyes with trabeculectomy-required APAC were recruited., Methods: Retinal oximetry was performed at postoperative day one and again at approximately 1 month. CT and the RNFL were tested on the same day. A paired t test and Pearson correlation were used for analysis., Results: Mean Sat O2 increased in retinal arterioles from 88.74% ± 14.36% at postoperative day 1 to 96.61% ± 18.42% at 1 month (p = 0.049). The mean diameter of the arterioles was statistically different between postoperative day 1 and 1 month (p = 0.044), as was the mean diameter of the venules (p = 0.027). APAC eyes at postoperative 1 month had a thinner mean CT, compared with day 1 (p = 0.002). No significant difference was found in the RNFL between postoperative day 1 and 1 month (p > 0.05). The Sat O2 in retinal arterioles correlated with the mean diameter of the arterioles at postoperative day 1 (r = -0.482, p = 0.020) and at 1 month (r = -0.463, p = 0.026). No significant correlation was found between retinal Sat O2 and other parameters., Conclusions: Increased Sat O2 in retinal arterioles, changed vessel diameter, and thinner CT from postoperative day 1 to 1 month suggest gradual recovery from APAC. However, the different pathophysiologies for APAC still need further study to prove., (Copyright © 2015 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Mitochondrial dysfunction contributing to the pathogenesis of glaucomatous neurodegeneration has stimulated considerable interest recently. In this study, we explored the role of peroxisome proliferator activated receptor-γ co-activator 1α (PGC-1α) in resveratrol-triggered mitochondrial biogenesis for preventing apoptosis in a retinal ganglion cell line RGC-5. Our results showed that serum deprivation induced cell apoptosis in a time-dependent manner. Applying resveratrol maintained the normal mitochondrial membrane potential, decreased the levels of both total and cleaved caspase-3, and inhibited the release of cytochrome c, which subsequently enhanced cell survival. Moreover, resveratrol stimulated mitochondrial biogenesis by increasing the absolute quantity of mitochondria as well as their DNA copies. Treatment with resveratrol promoted the protein expression of SIRT1, but not PGC-1α; instead, resveratrol facilitated PGC-1α translocation from the cytoplasm to the nucleus and up-regulated NRF1 and TFAM, which were blocked by nicotinamide. Collectively, we demonstrate that the SIRT1-dependent PGC-1α subcellular translocation following resveratrol application potentially attenuates serum deprivation-elicited RGC-5 cell death, thereby raising the possibility of mitigating glaucomatous retinopathy by enhancement of mitochondrial biogenesis.

Purpose: To examine the potential role of transient receptor potential canonical 6 (TRPC6) in the survival of retinal ganglion cells (RGCs) in the rat retinal ischemia/reperfusion (IR) model., Methods: TRPC6 expression in normal rat retina was analyzed by RT-PCR, Western blot analysis, in situ hybridization, and immunohistochemistry. The rat retinal IR model was established, and then the time course of TRPC6 expression was evaluated. Pharmacologic experiments were conducted. The expression of brain-derived neurotrophic factor (BDNF) was measured in the retinal IR model. Densities of surviving RGCs were estimated by counting fluorogold-labeled cells in 12 standard retinal areas., Results: TRPC6 mRNA and protein are selectively enriched in the RGC layer of the retina. A 60-minute interval of retinal ischemia could induce the elevation of TRPC6 mRNA and protein, both of which peaked 24 hours after reperfusion. TRPC6 protein expression decreased dramatically 1 week later, accompanied by substantial RGC loss. The TRPC channel's agonist significantly increased RGC survival, and the antagonist reduced cell density. The transcription level of the bdnf gene was enhanced at 24 hours; this paralleled the increase of TRPC6. When TRPC6 was blocked, the BDNF precursor (proBDNF), rather than its mature form (mBDNF), increased at 24 hours., Conclusions: This study documents the pattern of TRPC6 expression in the retinal IR model and provides evidence that activating TRPC channels before ischemia has early neuroprotective effects on RGCs in vivo. The protection of TRPC6 is BDNF mediated, and proBDNF-p75(NTR) signaling may contribute to the death of RGCs in retinal ischemia injury.

The P2X(7) receptor is associated with the death of many cell types, and growing evidence supports its presence on neurons. Activation of the P2X(7) receptor on isolated retinal ganglion cells increases intracellular calcium levels and can kill the cells. Within the intact eye, however, glia and other cell types surrounding the ganglion cells may provide protection and attenuate the effects of receptor stimulation. This investigation thus asks whether stimulation of the P2X(7) receptor can actually kill retinal ganglion cells in vivo. Drugs were injected intravitreally into the superior/nasal region of Long Evans rats. Cell survival was determined by counting the number of remaining ganglion cells labeled with aminostilbamidine. The P2X(7) receptor agonist BzATP reduced ganglion cell survival as compared to eyes injected with saline solution. Ganglion cell death was inhibited by co-injection of the P2X(7) antagonists Brilliant Blue G and MRS 2540. The loss of ganglion cells following activation of the P2X(7) receptor was also prevented by the adenosine A(3) adenosine receptor agonist MRS 3558. In conclusion, stimulation of the P2X(7) receptor can kill retinal ganglion cells in vivo. The neuroprotective effects of A(3) receptor activation identified in isolated ganglion cells are also apparent in vivo. This implies that the balance between extracellular ATP and its protective metabolite adenosine can influence ganglion cell survival in the living eye., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

The A(3) adenosine receptor is emerging as an important regulator of neuronal signaling, and in some situations receptor stimulation can limit excitability. As the NMDA receptor frequently contributes to neuronal excitability, this study examined whether A(3) receptor activation could alter the calcium rise accompanying NMDA receptor stimulation. Calcium levels were determined from fura-2 imaging of isolated rat retinal ganglion cells as these neurons possess both receptor types. Brief application of glutamate or NMDA led to repeatable and reversible elevations of intracellular calcium. The A(3) agonist Cl-IB-MECA reduced the response to both glutamate and NMDA. While adenosine mimicked the effect of Cl-IB-MECA, the A(3) receptor antagonist MRS 1191 impeded the block by adenosine, implicating a role for the A(3) receptor in response to the natural agonist. The A(1) receptor antagonist DPCPX provided additional inhibition, implying a contribution from both A(1) and A(3) adenosine receptors. The novel A(3) agonist MRS 3558 (1'S,2'R,3'S,4'R,5'S)-4-(2-chloro-6-(3-chlorobenzylamino)-9H-purin-9-yl)-2,3-dihydroxy-N-methylbicyclo [3.1.0] hexane-1-carboxamide and mixed A(1)/A(3) agonist MRS 3630 (1'S,2'R,3'S,4'R,5'S)-4-(2-chloro-6-(cyclopentylamino)-9H-purin-9-yl)-2,3-dihydroxy-N-methylbicyclo [3.1.0] hexane-1-carboxamide also inhibited the calcium rise induced by NMDA. Low levels of MRS 3558 were particularly effective, with an IC(50) of 400 pM. In all cases, A(3) receptor stimulation inhibited only 30-50% of the calcium rise. In summary, stimulation of the A(3) adenosine receptor by either endogenous or synthesized agonists can limit the calcium rise accompanying NMDA receptor activation. It remains to be determined if partial block of the calcium rise by A(3) agonists can modify downstream responses to NMDA receptor stimulation., (2009 Elsevier Ltd. All rights reserved.)

Purpose: To characterizes the progression of glaucoma in DBA/2J mice by measuring intraocular pressure (IOP) and retinal ganglion cells (RGCs) numbers in mice of various ages., Methods: A quantitative assessment of the pathophysiology of the DBA/2J mice was performed and the C57/BL6 mice was used as control. The IOP was measured by the servo-null micropipette system; the regional patterns of the loss of RGCs were determined by cell count of retrogradely-labeled RGCs., Results: The baseline IOP for DBA/2J mice at 7 weeks was (16.6 +/- 1.2)mm Hg. Then IOP increased extend to 12 months, with the peak of (25.2 +/- 1.2)mm Hg at 6 months of age. Retinal ganglion cell numbers did not decrease relative to control until 12 months of age (P = 0.006), when the loss was proportionally higher in peripheral regions (P < 0.05)., Conclusion: The elevation in IOP precedes the loss of RGCs by several months. RGCs cell loss occurs particularly in peripheral regions of the retina. These findings expand our understanding of the changes in DBA/2J mice and provide information for experiments design when they are used as a glaucoma model for future studies of RGCs degeneration in glaucoma.

Purpose: Adenosine can protect retinal ganglion cells from the death that accompanies a general ischemic challenge as well as excitotoxic death. In other tissues, both A1 and A3 adenosine receptor subtypes can mediate protection. While a role for the A1 adenosine receptor in ganglion cell protection has been established, a potential for the A3 receptor has only recently been proposed. Although the pharmacology is promising, the molecular identity of the responsible receptor is unclear as previous studies were unable to detect message for the A3 receptor in retinal ganglion cells. We combined laser capture microdisection (LCM) and immunopurification with traditional and real-time PCR to unequivocally demonstrate the presence of the A3 receptor message in rat retinal ganglion cells., Methods: Retinal ganglion cells of Long-Evans rat pups were retrograde labeled with aminostilbamidine. Eyeballs were enucleated, embedded, frozen, sectioned, and fluorescent cells in the ganglion cell layer were collected with LCM. Purified ganglion cells were also isolated with a two-step panning procedure. cDNA for the A3 receptor obtained from the microdissected ganglion cell layer, immunopurified ganglion cells, whole retina and testis was amplified using RT-PCR, confirmed by DNA sequencing and compared with published sequences. A3 receptor message was also amplified using real-time PCR. Ca2+ levels in immunopanned ganglion cells were measured ratiometrically with fura-2., Results: RNA from immunopurified ganglion cells and from dye-loaded cells in the ganglion cell layer contained message for the A3 receptor when amplified with either traditional RT-PCR or real-time PCR. The entire encoding region was sequenced and found to be 99% identical to the published code. The sequence closely resembled the consensus form of the gene, with other sequences deviating from this default code. Molecular identification was functionally confirmed in purified ganglion cells as the A3 receptor agonist Cl-IB-MECA prevented the excessive Ca2+ rise triggered by P2X7 agonist BzATP., Conclusions: Retinal ganglion cells express A3 adenosine receptor mRNA. Stimulation of this receptor can reduce the Ca2+ overload following excessive activation of P2X7 receptors.

The purines ATP and adenosine can act as a coordinated team of transmitters. As extracellular adenosine is frequently derived from the enzymatic dephosphorylation of released ATP, the distinct actions of the two purines can be synchronized. In retinal ganglion cells (RGCs), stimulation of the P2X7 receptor for ATP leads to increased intracellular Ca2+ and death. Here we define the contrasting effects of adenosine and identify protective actions mediated by the A3 receptor. Adenosine attenuated the rise in Ca2+ produced by the P2X7 agonist 3'-O-(4-benzoylbenzoyl)ATP (BzATP). Adenosine was also neuroprotective, increasing the survival of ganglion cells exposed to BzATP. The A3 adenosine receptor agonist 2-chloro-N6-(3-iodobenzyl)-adenosine-5'-N-methyluronimide (Cl-IB-MECA) mimicked the inhibition of the Ca2+ rise, whereas the A3 antagonist 3-Ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(+/-)-dihydropyridine-3,5-dicarboxylate (MRS-1191) reduced the protective effects of adenosine. Both Cl-IB-MECA and a second A3 receptor agonist IB-MECA reduced the cell loss triggered by BzATP. The actions of BzATP were mimicked by ATPgammaS, but not by ATP. In summary, adenosine can stop the rise in Ca2+ and cell death resulting from stimulation of the P2X7 receptor on RGCs, with the A3 adenosine receptor contributing to this protection. Hydrolysis of ATP into adenosine and perhaps inosine shifts the balance of purinergic action from that of death to the preservation of life.

Purpose: Retinal ganglion cells are known to express ionotropic P2X(7) receptors for ATP. Stimulation of these receptors in other cells can elevate Ca(2+) and sometimes lead to cell death. This study asked whether P2X(7) receptor stimulation alters the Ca(2+) levels and viability of retinal ganglion cells., Methods: P2X(7) agonists were applied to retinal ganglion cells from neonatal rats loaded with fura-2 to examine their effect on intracellular Ca(2+) levels. The effect of P2X(7) receptor stimulation on cell viability was examined in rat retinal ganglion cells back-labeled with aminostilbamidine., Results: The P2X(7) agonist benzoylbenzoyl adenosine triphosphate (BzATP) led to a large, sustained increase in Ca(2+). BzATP was >100-fold more effective than ATP at raising intracellular Ca(2+), when both agonists were applied at 10 microM. The response to BzATP was enhanced threefold by removal of extracellular Mg(2+), was dependent on extracellular Ca(2+), and was prevented by brilliant blue G (BBG). BzATP led to a concentration-dependent reduction in the number of cells with a median lethal dose (LD(50)) of 35 muM. Cell death was prevented by the P2X(7) antagonists BBG and oxidized ATP, but not by 30 microM suramin, consistent with the actions of the P2X(7) receptor. BzATP activated caspases in ganglion cells, but did not lead to membrane blebbing or increased permeability to Yo-Pro-1. The L-type Ca(2+) channel blocker nifedipine attenuated cell death, suggesting excessive Ca(2+) influx contributes to the lethal effects of BzATP., Conclusion: Short-term stimulation of the P2X(7) receptor can raise Ca(2+) in rat retinal ganglion cells, whereas sustained stimulation of the receptor can kill them.

Background The result of primary open-angle glaucoma is the loss of retinal ganglion cells. Transient receptor potential cation channel 6 is a pressure-related channel that may function in the survival of retinal ganglion cells. The purpose of this study was to evaluate the expression levels of the transient receptor potential cation channel 6 gene in patients with primary open-angle glaucoma. Design Randomization study at Zhongshan Ophthalmic Center in China. Participants 80 primary open-angle glaucoma patients and 75 cataract patients recruited from Zhongshan Ophthalmic Center. Methods Total RNA was extracted from the leukocytes of the peripheral blood collected. The levels of transient receptor potential cation channel 6-messenger RNA were determined by real-time polymerase chain reaction. Related factors including age, intraocular pressure, optic cup-to-disc ratio and visual field defect were analysed accordingly. Main Outcome Measures Clinical examination and the messenger RNA level. Results The expression level of the transient receptor potential cation channel 6 gene in the leukocytes of primary open-angle glaucoma patients was two times higher when compared with control cataract patients. The gene expression level was also correlated with intraocular pressure and cup-to-disc ratio. Treatment with different anti-glaucoma drugs did not affect the gene expression. Conclusions Increasing expression levels of the transient receptor potential cation channel 6 gene in the blood accompanies chronic elevation of intraocular pressure in primary open-angle glaucoma and may serve as a genetic biomarker for primary open-angle glaucoma. [ABSTRACT FROM AUTHOR]

Abstract: Glaucoma, as characterized by accelerated retinal ganglion cell (RGC) death and cupping of optic nerve head (ONH), is one of the leading causes of blindness worldwide. Elevated intraocular pressure (IOP) is generally considered as a major risk factor in the pathogenesis of glaucoma. Previous studies showed that glaucoma caused decrease in collagen and elastin density in several ocular tissues, such as lamina cribrosa, peripapillary sclera and cornea, and resulted in reduced elasticity and compliance of these tissues. It is known that estrogen has protective effects against glaucoma, yet the underlying mechanism still remains obscure. Prior researches have provided evidences showing that the estrogen receptors (ERs) express in a variety of the ocular tissues. Estrogen activates the synthesis of collagen fiber and improves the compliance of these tissues. This leads to a reasonable postulation that increased estrogen may result in a higher content of the collagen fibers and enhanced flexibility of the whole eye, which would therefore decrease IOP. Particularly, the increase in the amounts of collagen fibers at lamina cribrosa improves its compliance, which in turn relieves its compression on RGC axons. Therefore, even at the same IOP level, the softening of cribriform foramina yields a more flexible environment for the RGCs to survive. We therefore hypothesize that estrogen at proper dosage can be considered as a potential therapy for glaucoma since it is able to prevent the eye from glaucomatous damage and lower IOP, especially for those menopausal women with glaucoma. [Copyright &y& Elsevier]

Abstract: While the death of retinal ganglion cells in glaucoma is frequently associated with an elevation of intraocular pressure (IOP), the mechanisms connecting the two processes remain unclear. Extracellular ATP is released throughout the body in response to mechanical deformations. We have previously shown that patients with an acute rise in IOP have an elevated concentration of ATP in the anterior chamber. In the present study we ask whether ATP levels remain increased in patients with chronic elevations of IOP. The concentration of ATP in samples of aqueous humor obtained from patients with primary chronic angle-closure glaucoma (PCACG) was compared with that from control cataract patients whose IOP was normal. The mean ATP concentration in aqueous humor was 14-fold higher for PCACG samples than for control. ATP levels were correlated with IOP and the cup-to-disk ratio (C/D ratio). Brief treatment of Timolol, Alphagan, Pilocarpine and/or Azopt did not affect the rise in ATP concentration. In conclusion, sustained elevations in extracellular ATP levels accompany the chronic elevation of IOP in chronic glaucoma. As numerous ocular tissues express purinergic receptors, an increased extracellular ATP may have diverse physiological and pathophysiological effects. [Copyright &y& Elsevier]

Retinal ganglion cells process the visual signal and transmit it along their axons in the optic nerve to the brain. Molecular, immunohistochemical, and functional analyses indicate that the majority of retinal ganglion cells express the ionotropic P2X7 receptor. Stimulation of the receptor can lead to a rise in intracellular calcium and cell death, although death does not involve the opening of a large diameter pore. Adenosine acting at A3 receptors can attenuate the rise in calcium and death accompanying P2X7 receptor activation, suggesting that dephosphorylation of ATP into adenosine is neuroprotective and that the balance of extracellular purines can influence neuronal survival. Increased intraocular pressure can lead to release of excessive extracellular ATP in the retina and damage ganglion cells by acting on P2X7 receptors, implicating a role for the receptor in the loss of ganglion cell activity in glaucoma. In summary, the activation of P2X7 receptors has both physiologic and pathophysiologic implications for ganglion cell function. These characteristics may also provide an insight into the contributions the P2X7 receptor makes to neurons elsewhere. [ABSTRACT FROM AUTHOR]

Retinal ganglion cells process the visual signal and transmit it along their axons in the optic nerve to the brain. Molecular, immunohistochemical, and functional analyses indicate that the majority of retinal ganglion cells express the ionotropic P2X7 receptor. Stimulation of the receptor can lead to a rise in intracellular calcium and cell death, although death does not involve the opening of a large diameter pore. Adenosine acting at A3 receptors can attenuate the rise in calcium and death accompanying P2X7 receptor activation, suggesting that dephosphorylation of ATP into adenosine is neuroprotective and that the balance of extracellular purines can influence neuronal survival. Increased intraocular pressure can lead to release of excessive extracellular ATP in the retina and damage ganglion cells by acting on P2X7 receptors, implicating a role for the receptor in the loss of ganglion cell activity in glaucoma. In summary, the activation of P2X7 receptors has both physiologic and pathophysiologic implications for ganglion cell function. These characteristics may also provide an insight into the contributions the P2X7 receptor makes to neurons elsewhere. [ABSTRACT FROM AUTHOR]