Inhibition of NLRP3 inflammasome by MCC950 under hypoxia alleviates photoreceptor apoptosis via inducing autophagy in Müller glia.

NLRP3 inflammasome activation has emerged as a critical initiator of inflammatory response in ischemic retinopathy. Here, we identified the effect of a potent, selective NLRP3 inhibitor, MCC950, on autophagy and apoptosis under hypoxia. Neonatal mice were exposed to hyperoxia for 5 days to establish oxygen-induced retinopathy (OIR) model. Intravitreal injection of MCC950 was given, and then autophagy and apoptosis markers were assessed. Retinal autophagy, apoptosis, and related pathways were evaluated by western blot, immunofluorescent labeling, transmission electron microscopy, and TUNEL assay. Autophagic activity in Müller glia after NLRP3 inflammasome inhibition, together with its influence on photoreceptor death, was studied using western blot, immunofluorescence staining, mRFP-GFP-LC3 adenovirus transfection, cell viability, proliferation, and apoptosis assays. Results showed that activation of NLRP3 inflammasome in Müller glia was detected in OIR model. MCC950 could improve impaired retinal autophagic flux and attenuate retinal apoptosis while it regulated the retinal AMPK/mTOR/ULK-1 pathway. Suppressed autophagy and depressed proliferation capacity resulting from hypoxia was promoted after MCC950 treatment in Müller glia. Inhibition of AMPK and ULK-1 pathway significantly interfered with the MCC950-induced autophagy activity, indicating MCC950 positively modulated autophagy through AMPK/mTOR/ULK-1 pathway in Müller cells. Furthermore, blockage of autophagy in Müller glia significantly induced apoptosis in the cocultured 661W photoreceptor cells, whereas MCC950 markedly preserved the density of photoreceptor cells. These findings substantiated the therapeutic potential of MCC950 against impaired autophagy and subsequent apoptosis under hypoxia. Such protective effect might involve the modulation of AMPK/mTOR/ULK-1 pathway. Targeting NLRP3 inflammasome in Müller glia could be beneficial for photoreceptor survival under hypoxic conditions.

Molecular cloning of the hepcidin gene from crescent sweetlips (Plectorhinchus cinctus) and characterization of its encoded antimicrobial peptide.

Hepcidin has been identified as an important antimicrobial peptide exerting important innate immunomodulatory activities in many fish species. In the present study, reverse transcription PCR coupled with the rapid amplification of cDNA ends was used to obtain the full-length cDNA of the crescent sweetlips hepcidin gene, which is 829 bp in length and includes an 273 bp ORF encoding a peptide with 90 amino acid residues. Sequence alignment showed a typical RXKR motif and eight conserved cysteine residues in the deduced amino acid sequences. Four disulfide bonds were predicted to form between these eight cysteines, which may stabilize the hairpin structure in hepcidin molecule. Furthermore, phylogenetic analysis showed that the deduced amino acid sequences of crescent sweetlips hepcidin had high sequence homology to hepcidins from fish species of Eupercaria. In addition, the crescent sweetlips hepcidin peptide demonstrated a strong antimicrobial activity in vitro against several types of pathogenic bacteria in fish. In conclusion, the obtained results suggested that crescent sweetlips hepcidin possessed the typical structure similar to other fish hepcidins and had strong antibacterial activity, which showed great potential in the prevention of fish diseases in aquaculture.

TLR4 Inhibition Protects against Retinal Ganglion Cell Damage in Rats with Chronic Ocular Hypertension.

BACKGROUND: This study aims to investigate the protective effect of Toll-like receptor 4 (TLR4) inhibitor Resatorvid (TAK-242) on retinal ganglion cells (RGCs) in a chronic ocular hypertension (COH) rat model, as well as to explore the potential involved mechanisms. METHODS: COH model was built up in rats with a single intracameral administration of cross-linking hydrogel. The expression levels of TLR4, NLR family pyrin domain containing 3 (NLRP3), microglial activation and pro-inflammatory cytokines were evaluated in COH retinas and COH retinas treated with TAK-242 using immunofluorescence staining and Western blot. Additionally, retrograde labeling and neuronal nuclear protein (NeuN) staining were performed to count RGCs. RESULTS: Activated microglia and increased TLR4 expression were observed in the retinas of COH rats. This was accompanied by upregulated expressions of NLRP3, tumor necrosis factor alpha (TNF-α), cytokine interleukin-1ß (IL-1ß) and Interleukin-6 (IL-6). Intravitreal injection of TAK-242 promoted the survival of RGCs by attenuating microglial activation, interfering with the TLR4-NLRP3 pathway and regulating pro-inflammatory cytokines. CONCLUSIONS: Targeting TLR4 inhibition could be a potential therapeutic strategy to protect RGCs from COH damage.

Prokaryotic Expression, Purification, and Antibacterial Activity of the Hepcidin Peptide of Crescent Sweetlips (Plectorhinchus cinctus).

The hepcidin peptide of crescent sweetlips (Plectorhinchus cinctus) is a cysteine-rich, cationic antimicrobial peptide that plays a crucial role in the innate immune system's defense against invading microbes. The aim of this study was to identify the optimal parameters for prokaryotic expression and purification of this hepcidin peptide and characterize its antibacterial activity. The recombinant hepcidin peptides were expressed in Escherichia coli strain Arctic Express (DE3), with culture and induction conditions optimized using response surface methodology (RSM). The obtained hepcidin peptides were then purified before tag cleavage, and their antibacterial activity was determined. The obtained results revealed that induction temperature had the most significant impact on the production of soluble recombinant peptides. The optimum induction conditions were determined to be an isopropylthio-ß-galactoside (IPTG) concentration of 0.21 mmol/L, induction temperature of 18.81 °C, and an induction time of 16.01 h. Subsequently, the recombinant hepcidin peptide was successfully purified using Ni-IDA affinity chromatography followed by SUMO protease cleavage. The obtained hepcidin peptide (without His-SUMO tag) demonstrated strong antimicrobial activity in vitro against V. parahaemolyticus, E. coli, and S. aureus. The results showed prokaryotic (E. coli) expression is a feasible way to produce the hepcidin peptide of crescent sweetlips in a cost-effective way, which has great potential to be used as an antimicrobial agent in aquaculture.

Clinical Efficacy of Preoperative and Intraoperative Intravitreal Ranibizumab as Adjuvant Therapy of Ahmed Glaucoma Valve Implantation Combined with Vitrectomy in the Management of Neovascular Glaucoma with Diabetic Vitreous Hemorrhage.

Neovascular glaucoma (NVG) secondary to proliferative diabetic retinopathy (PDR) is a devastating ocular disease with poor prognosis. Intravitreal ranibizumab injection (IVR) has been used as adjuvant therapy of surgical interventions preoperatively or intraoperatively. This study aimed to determine the efficacy and safety of combined IVR as adjuvant therapy in treating NVG with vitreous hemorrhage (VH) in PDR. A total of 39 NVG patients with VH (39 eyes) received IVR 3 to 5 days before surgery, and then they were assigned to either pars plana vitrectomy (PPV) + Ahmed glaucoma valve (AGV) implantation (Group 1, n = 22) or PPV + AGV implantation + intraoperative IVR (Group 2, n = 17). Patients were followed up for at least 9 months. Intraocular pressure (IOP), anti-glaucoma medications, best corrected visual acuity (BCVA), surgical success rates and postoperative complications were compared. Results showed that IOP decreased promptly after surgery and was notably maintained at a mid-term follow-up in both groups, and no significant differences were observed (all p > 0.05). Additional intraoperative IVR significantly reduced postoperative recurrent VH and iris neovascularization (p = 0.047, p = 0.025, respectively). There was no remarkable difference in postoperative anti-glaucoma medications, BCVA and complications between two groups (all p > 0.05). In conclusion, preoperative and intraoperative IVR as adjuvant therapy of AGV implantation combined with PPV could be a safe and effective treatment for NVG with VH in PDR. An additional intraoperative anti-VEGF injection could significantly reduce postoperative VH and iris neovascularization.

Inhibition of vascular endothelial growth factor alleviates neovascular retinopathy with regulated neurotrophic/proinflammatory cytokines through the modulation of DBI-TSPO signaling.

Diazepam binding inhibitor (DBI)-translocator protein (18kDa) (TSPO) signaling in the retina was reported to possess coordinated macroglia-microglia interactions. We investigated DBI-TSPO signaling and its correlation with vascular endothelial growth factor (VEGF), neurotrophic or inflammatory cytokines in neovascular retinopathy, and under hypoxic conditions. The vitreous expression of DBI, VEGF, nerve growth factor (NGF), and interleukin-1beta (IL-1ß) were examined in proliferative diabetic retinopathy (PDR) patients with or without anti-VEGF therapy and nondiabetic controls. Retinal DBI-TSPO signaling and the effect of the anti-VEGF agent were evaluated in a mouse model of oxygen-induced retinopathy (OIR). Interactions between Müller cell-derived VEGF and DBI, as well as cocultured microglial cells under hypoxic conditions, were studied, using Western blot, real-time RT-PCR, enzyme-linked immunosorbent assay (ELISA), flow cytometry, and immunofluorescent labeling. Results showed that vitreous levels of DBI, VEGF, NGF, and IL-1ß were significantly higher in PDR patients compared with controls, which further changed after anti-VEGF therapy. A statistical association was found between vitreous DBI and VEGF, NGF, IL-1ß, and age. The application of the anti-VEGF agent in the OIR model induced retinal expression of DBI and NGF, and attenuated inflammation and microglial cell activation. Inhibition of Müller cell-derived VEGF could increase its DBI expression under hypoxic conditions, while the DBI-TSPO signaling pathway is essential for anti-VEGF agents exerting anti-inflammatory and neuroprotective effects, as well as limiting inflammatory magnitude, promoting its neurotrophin production and anti-inflammatory (M2) polarization in microglial cells. These findings suggest the beneficial effect of anti-VEGF therapy on inflammation and neurotrophy of retinal glial cells through modulation of the DBI-TSPO signaling pathway.

Quantitative evaluation of retinal and choroidal changes in Fabry disease using optical coherence tomography angiography.

To examine the retinal and choroidal changes in patients with Fabry disease (FD) using optical coherence tomography angiography (OCTA). FD patients and age- and sex-matched healthy subjects were enrolled. A detailed ophthalmological examination was performed for all participants. The retinal thickness, ganglion cell layer with inner plexiform layer (GCIPL) thickness, choroidal thickness (CT), vessel length density (VLD), vessel perfusion density (VPD), and foveal avascular zone (FAZ) were analyzed in a detailed way with OCTA. Moreover, all FD patients underwent several laboratory tests to evaluate systemic conditions. A total of 54 subjects comprising 26 FD patients and 28 normal controls were enrolled. The retinal thickness, GCIPL thickness, and FAZ area showed no significant differences between the two groups (all P > 0.05). Only the superior CT in FD patients was significantly thinner than that in the normal subjects (P = 0.040). The macular VLD and VPD in the FD group were significantly reduced compared with the healthy controls (P = 0.026, P = 0.008). The macular VLD in FD patients had no significant correlations with different laboratory results (all P > 0.05), while the macular VPD were negatively correlated with creatinine (r = - 0.432, P = 0.028) and cystatin C (r = - 0.422, P = 0.032). FD patients may have retinal vascular dropout and choroidal vascular alterations. Analysis of vessel density using OCTA might be useful in the clinical assessment in FD patients.

Iris metastasis of diffuse large B-cell lymphoma misdiagnosed as primary angle-closure glaucoma: A case report and review of the literature.

BACKGROUND: Lymphoma with intraocular metastasis is an uncommon and serious disease. We describe a case of diffuse large B-cell lymphoma (DLBCL) with iris metastasis. Meanwhile, we refer to published case reports retrieved via a PubMed search to summarize this rare disease. CASE PRESENTATION: Glaucoma and uveitis symptoms were found in the left eye of a 50-year-old woman upon admission to the hospital. After treatment and pathological examination, the iris of her left eye was diagnosed with DLBCL. Given the patient's unfavorable treatment options in the local hospital, primary enucleation was offered as a therapeutic option. CONCLUSIONS: Iris metastasis of systemic lymphoma is an extremely rare ophthalmic disease with poor prognosis. Ophthalmologists should be able to definitively and differentially diagnose eye symptoms and pay attention to systemic conditions to provide a series of optimized treatments.

Analysis of Plasma Hydrogen Sulfide, Homocysteine, and L-Cysteine in Open-Angle Glaucoma Patients.

Purpose: To compare the plasma levels of hydrogen sulfide (H2S), homocysteine (Hcy), and L-cysteine (Cys) among primary open-angle glaucoma (POAG), normal tension glaucoma (NTG), ocular hypertension (OHT), and normal individuals. To explore associated factors and evaluate their diagnostic abilities in glaucoma. Methods: POAG, NTG, OHT, and normal subjects were recruited from Ruijin Hospital between December 2016 and December 2018. All subjects underwent thorough ophthalmological examinations, and fasting venous blood was taken to determine the concentrations of H2S, Hcy, and Cys. Results: Forty-two POAG, 20 NTG, 52 OHT, and 78 controls were enrolled. The H2S levels in POAG group were significantly lower than those in OHT group (P = 0.036) and normal group (P < 0.001), while the Hcy and Cys levels in POAG and NTG groups were significantly higher (P = 0.007-0.043). The concentrations of H2S, Hcy, and Cys in glaucoma patients with different stages were not significantly different (all P > 0.05). POAG patients with longer duration of diagnosis had lower concentrations (P = 0.026, P = 0.001, P < 0.001), but no significant differences in NTG patients (all P > 0.05). The Hcy and Cys levels in NTG patients showed negative but weak correlations with mean deviation (r = -0.450, P = 0.047; r = -0.478, P = 0.033). All these concentrations showed significant but poor diagnostic values in POAG-Normal group [area under curve (AUC) = 0.642-0.721, P < 0.05]. The H2S level showed poor diagnostic power in POAG-OHT group (AUC = 0.657, P < 0.01). Conclusion: Decreased levels of H2S and increased levels of Hcy and Cys may be associated with glaucoma, especially in POAG. However, the H2S/Hcy metabolic pathway is not sufficiently sensitive to be used as a reliable biomarker in glaucoma.

Clinical efficacy of Ahmed glaucoma valve implantation combined with 23-gauge vitrectomy for medically uncontrolled neovascular glaucoma with proliferative diabetic retinopathy.

AIM: To describe the clinical results of combined Ahmed valve implantation and 23-gauge vitrectomy for medically uncontrolled neovascular glaucoma (NVG) secondary to proliferative diabetic retinopathy (PDR). METHODS: The medical records of medically uncontrolled NVG patients with PDR who underwent Ahmed valve implantation and 23-gauge vitrectomy between March 2016 and December 2018 were reviewed. Enrolled patients had at least 6-month follow-up. Panretinal photocoagulation (PRP), anti-vascular endothelial growth factor, surgery and medication history were documented. RESULTS: Eleven eyes of 11 patients were included in our study. The visual acuity improved in 8 eyes and remained unchanged in 3 eyes. The preoperative intraocular pressure (IOP) was significantly decreased at the last follow-up (48.8±4.3 to 17.0±1.5 mm Hg, P<0.001). All eyes needed three topical anti-glaucomatous medications before surgery, but the number was significantly reduced to 0.72±0.19 at the last visit (P<0.001). Four eyes had choroidal detachment and 3 eyes had minor hyphemia, all of which gradually resolved without treatments in one week. CONCLUSION: Ahmed glaucoma valve implantation combined with 23-gauge vitrectomy might be a safe and alternative treatment for NVG with PDR.

Intravitreal Conbercept Injection as an Adjuvant in Vitrectomy with Silicone Oil Infusion for Severe Proliferative Diabetic Retinopathy.

Purpose: To assess the clinical effects of preoperative, intraoperative, or preoperative combined with intraoperative intravitreal conbercept (IVC) injection in vitrectomy with silicone oil tamponade for severe proliferative diabetic retinopathy (PDR). Methods: Ninety-eight eyes of 98 severe PDR patients undergoing vitrectomy with silicone oil tamponade were randomly assigned to 3 groups: Group 1 (34 eyes) received IVC injections 3 to 5 days before surgery; Group 2 (35 eyes) received IVC injections at the end of surgery; and Group 3 (29 eyes) received IVC injections 3 to 5 days before and at the end of operation. Follow-up examinations were performed for 6 months. Results: The incidence and severity of intraoperative bleeding were not significantly different (P = 0.233). However, the duration of surgery was significantly shorter in Group 1 and Group 3 compared with Group 2 (P < 0.001). The incidences of early and late recurrent vitreous hemorrhage (VH) were 32.35%, 28.57%, and 13.80%, respectively. At 6-month follow-up, mean best-corrected visual acuity had significantly increased to 1.25 ± 0.45 logMAR in Group 1, 1.29 ± 0.46 logMAR in Group 2, 1.16 ± 0.44 logMAR in Group 3 (all P < 0.001). The incidence of postoperative VH, neovascular glaucoma, and retinal detachment in Group 3 was slightly lower, however, no significant differences were observed (all P > 0.05). In young patients, similar results were observed and Group 3 had better visual improvements (P = 0.037). Conclusions: Preoperative IVC injection could be a safe and effective adjunct in pars plana vitrectomy with silicone oil tamponade for severe PDR. Preoperative combined with intraoperative IVC are promising, especially in young patients.

Extracellular Signal-Regulated Kinase 1/2 Pathway Is Insufficiently Involved in the Neuroprotective Effect by Hydrogen Sulfide Supplement in Experimental Glaucoma.

Purpose: Glaucoma is a neurodegenerative eye disease characterized by gradually impaired visual field and irreversible blindness due to retinal ganglion cell (RGC) loss. Our previous studies have confirmed that hydrogen sulfide (H2S) takes part in the glaucomatous process and contributes to RGC protection. The present study aimed to further investigate the role of extracellular signal-regulated kinase 1/2 (ERK 1/2) pathway underlying the impact of H2S, to better understand the mechanism through which H2S exerts neuroprotection in glaucoma. Methods: An established rat glaucoma model was used and 168 rats were qualified to undergo sodium hydrosulfide (NaHS, a H2S donor)/PD98059 (an ERK inhibitor) treatment. Then the survival and apoptosis of RGC were evaluated through retrograde labeling and TUNEL staining, along with activity evaluations of ERK 1/2 pathway, intrinsic apoptotic pathway, glial activation, nuclear factor kappa B (NF-κB) pathway, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, autophagy, and TNF-α production through immunohistochemistry, Western blotting, and ELISA. Results: The study demonstrated that NaHS suppressed ERK 1/2 pathway activity similarly to PD98059 in retinas of experimental glaucoma rats, while PD98059 also similarly suppressed glial activation, NF-κB pathway, NADPH oxidase, and TNF-α production. However, PD98059 did not affect RGC survival, apoptotic regulation, or autophagy as NaHS did. Conclusions: Our study indicated that inhibition of ERK 1/2 pathway might partly contribute to the neuroprotection by H2S in experimental glaucoma; however, it was insufficient to initiate the therapeutic effect on its own.

Intravitreal ranibizumab or conbercept for retinal arterial macroaneurysm: a case series.

BACKGROUND: There is no consensus for the standard treatment of retinal arterial macroaneurysm (RAM). Intravitreal anti-vascular endothelium growth factor (anti-VEGF) is an alternative treatment option for RAM. The purpose of this study is to describe the clinical efficacy of intravitreal ranibizumab or intravitreal conbercept for retinal arterial macroaneurysm. CASE PRESENTATION: Three cases that presented with symptomatic RAM were treated with intravitreal anti-VEGF agents. Two eyes received two intravitreal ranibizumab injections with a time interval of one month and completed a one-year follow-up, while one eye only received one intravitreal conbercept injection and was followed up for six months. Both the retinal thickness and the visual acuity were significantly improved at the final clinic visit. The macular hemorrhage and edema were resolved. There were no ocular or systemic side effects. CONCLUSIONS: Intravitreal ranibizumab or conbercept might be used as a therapeutic option for symptomatic retinal arterial macroaneurysm patients. Anti-VEGF therapy should be further investigated in a larger series with longer follow-up for this disease profile.

Primary vitreoretinal natural killer/T-cell lymphoma with breast involvement: A case report and review of the literature.

A 50-year-old woman developed recurrent vitreous opacities in her left eye. The first diagnostic vitrectomy revealed no significant abnormality. Optical coherence tomography showed multiple high-density reflective nodules. The ratio of interleukin-6 to interleukin-10 was over 1 in her aqueous humor, and Epstein-Barr virus was present. A conventional immunohistochemistry examination of vitrectomy specimens was diffusely positive for CD2, CD3, and Ki-67. Highly metabolic nodules were found in her right breast on positron emission tomography-computed tomography scan. Immunohistochemistry of the breast biopsy was suggestive of natural killer/T-cell lymphoma. Considering the homology between the two lesions, combined with ancillary cytokine, cytology, and flow cytometry findings, the final diagnosis was primary vitreoretinal natural killer/T-cell lymphoma with involvement of the breast. The lymphoma resolved with chemotherapy, intravitreal injection of methotrexate, and ocular radiotherapy. This case shows that primary vitreoretinal natural killer/T-cell lymphoma can present with concomitant systemic involvement. We reviewed relevant published literature and summarized some new approaches that make the diagnosis easier and faster; however, the cytopathologic analysis of intraocular fluid is irreplaceable. An effective treatment strategy is still a matter of speculation.

Effect of Adenosine and Adenosine Receptor Antagonists on Retinal Müller Cell Inwardly Rectifying Potassium Channels under Exogenous Glutamate Stimulation.

The vitreousness of glaucoma subjects contains elevated glutamate, and excessive extracellular glutamate is toxic to retinal neurons. Therefore, glutamate clearance is potentially impaired in the retina of glaucoma subjects. Müller cells play an important role in maintaining low extracellular levels of neurotransmitters, such as glutamate. A better understanding of the cross-talk between adenosine and glutamate may provide a better characterization of the regulatory network in Müller cells. Here, Müller cells were purified from the rat retina on postnatal day 5 using the papain digestion method. Application of increasing concentrations of glutamate (0-20 mmol/L) caused a dose-dependent decrease in the expression levels of Kir4.1, Kir2.1, GLAST, and GS. Exogenous adenosine regulated Kir channels and subsequently promoted GLAST and GS expression levels in Müller cells under exogenous glutamate stimulation. These effects were partly dependent on adenosine receptors.

Surgical removal of submacular perfluorocarbon liquid with a 38-gauge flexible cannula combined with internal limiting membrane peeling and intravitreal air tamponade: a case series.

BACKGROUND: To report a case series in which a modified technique was used to remove retained submacular perfluorocarbon liquid (PFCL) secondary to vitreoretinal surgery for rhegmatogenous retinal detachment. CASE PRESENTATION: Four patients who had undergone pars plana vitrectomy for rhegmatogenous retinal detachment were further treated with surgical intervention because of retained submacular PFCL. With a three-port pars plana approach, after the internal limiting membrane peeling with indocyanine green staining, a 38-gauge flexible cannula was used to aspirate the submacular perfluorocarbon bubble, followed by fluid-air exchange and air injection into vitreous cavity. Submacular perfluorocarbon liquid was removed successfully and visual acuity had an improvement in all cases. CONCLUSION: The surgical removal of retained submacular PFCL using a 38-gauge flexible cannula combined with internal limiting membrane peeling and intravitreal air tamponade may provide anatomical and visual satisfactory outcomes.

Hydrogen sulfide supplement attenuates the apoptosis of retinal ganglion cells in experimental glaucoma.

Glaucoma is a group of neurodegenerative eye diseases characterized by progressive impairment of visual function due to loss of retinal ganglion cells (RGC). As hydrogen sulfide (H2S) was reported to play a role in the process of glaucomatous neuropathy and improve RGC survival in experimental glaucoma, the authors aimed to investigate the anti-apoptosis effect of H2S supplement in a rat glaucoma model, and further tried to explore the involved factors in the neuroprotection. A chronic ocular hypertension (COH) rat model induced by intracameral injection of cross-linking hydrogel was employed to simulate glaucoma and 288 rats were subjected to experimental procedures in the present study. After 4 weeks of sodium hydrosulfide (NaHS) administration following COH induction, the apoptosis of RGC isolated from experimented rats as well as apoptosis of neurons in ganglion cell layer (GCL), intrinsic apoptotic pathway activity, mitochondrial function, glial activation, NF-κB pathway activity, NADPH oxidase activity, autophagy activity and TNF-α level in retina were evaluated. The results showed that H2S supplement effectively attenuated the apoptosis of RGC in experimental glaucoma, and the neuroprotection by H2S might correlate with preservation of mitochondrial function, attenuation of oxidative stress, suppression of glial activation, inhibition of inflammatory pathways and downregulation of autophagy. Our study indicated that H2S supplement resulted in significant neuroprotection through attenuation of RGC apoptosis which might be linked with multiple factors in experimental glaucoma. The new therapeutic strategy might potentially contribute to benefit glaucoma treatment, which is worth further concerns.

Relevant variations and neuroprotecive effect of hydrogen sulfide in a rat glaucoma model.

Glaucoma is an irreversible and blinding neurodegenerative disease of the eye, and is characterized by progressive loss of retinal ganglion cells (RGCs). Since endogenous hydrogen sulfide (H2S) was reported to be involved in neurodegeneration in the central nervous system, the authors aimed to develop a chronic ocular hypertension (COH) rat model simulating glaucoma and therein test the H2S level together with the retinal protein expressions of related synthases, and further investigated the effect of exogenous H2S supplement on RGC survival. COH rat model was induced by cross-linking hydrogel injection into anterior chamber, and the performance of the model was assessed by intraocular pressure (IOP) measurement, RGC counting and retinal morphological analysis. Endogenous H2S level was detected along with the retinal protein expressions of H2S-related synthases cystathionine ß-synthase (CBS), cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3-MST) in the COH rats. Retinal H2S level and RGC survival were evaluated again after NaHS (a H2S donor) treatment in the COH rats. The results showed that the COH model succeeded in simulating glaucoma features, and retinal H2S level decreased significantly when the retinal protein expressions of CBS, CSE and 3-MST were downregulated generally in the COH rats. Furthermore, the decrease of retinal H2S level and loss of RGCs were both improved by NaHS treatment in experimental glaucoma, without obvious variation of IOP. Our study revealed that the intracameral injection of cross-linking hydrogel worked efficiently in modeling glaucoma, and H2S had protective effect on RGCs and might be involved in the pathological mechanism of glaucomatous neuropathy.