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Abstract The retina is part of the central nervous system (CNS). Neurons in the CNS and retinal ganglion cells lack the ability to regenerate axons spontaneously after injury. The intrinsic axonal growth regulators, their interaction and roles that enable or inhibit axon growth are still largely unknown. This study endeavored to characterize the molecular characteristics under neurodegenerative and regenerative conditions. Data-Independent Acquisition Mass Spectrometry was used to map the comprehensive proteome of the regenerative retina from 14-day-old mice (Reg-P14) and adult mice after lens injury (Reg-LI) both showing regrowing axons in vitro, untreated adult mice, and retina from adult mice subjected to two weeks of elevated intraocular pressure showing degeneration. A total of 5750 proteins were identified (false discovery rate

Abstract Background NADPH oxidase (NOX), a primary source of endothelial reactive oxygen species (ROS), is considered a key event in disrupting the integrity of the blood-retinal barrier. Abnormalities in neurovascular-coupled immune signaling herald the loss of ganglion cells in glaucoma. Persistent microglia-driven inflammation and cellular innate immune system dysregulation often lead to deteriorating retinal degeneration. However, the crosstalk between NOX and the retinal immune environment remains unresolved. Here, we investigate the interaction between oxidative stress and neuroinflammation in glaucoma by genetic defects of NOX2 or its regulation via gp91ds-tat. Methods Ex vivo cultures of retinal explants from wildtype C57BL/6J and Nox2 −/− mice were subjected to normal and high hydrostatic pressure (Pressure 60 mmHg) for 24 h. In vivo, high intraocular pressure (H-IOP) was induced in C57BL/6J mice for two weeks. Both Pressure 60 mmHg retinas and H-IOP mice were treated with either gp91ds-tat (a NOX2-specific inhibitor). Proteomic analysis was performed on control, H-IOP, and treatment with gp91ds-tat retinas to identify differentially expressed proteins (DEPs). The study also evaluated various glaucoma phenotypes, including IOP, retinal ganglion cell (RGC) functionality, and optic nerve (ON) degeneration. The superoxide (O2 -) levels assay, blood-retinal barrier degradation, gliosis, neuroinflammation, enzyme-linked immunosorbent assay (ELISA), western blotting, and quantitative PCR were performed in this study. Results We found that NOX2-specific deletion or activity inhibition effectively attenuated retinal oxidative stress, immune dysregulation, the internal blood-retinal barrier (iBRB) injury, neurovascular unit (NVU) dysfunction, RGC loss, and ON axonal degeneration following H-IOP. Mechanistically, we unveiled for the first time that NOX2-dependent ROS-driven pro-inflammatory signaling, where NOX2/ROS induces endothelium-derived endothelin-1 (ET-1) overexpression, which activates the ERK1/2 signaling pathway and mediates the shift of microglia activation to a pro-inflammatory M1 phenotype, thereby triggering a neuroinflammatory outburst. Conclusions Collectively, we demonstrate for the first time that NOX2 deletion or gp91ds-tat inhibition attenuates iBRB injury and NVU dysfunction to rescue glaucomatous RGC loss and ON axon degeneration, which is associated with inhibition of the ET-1/ERK1/2-transduced shift of microglial cell activation toward a pro-inflammatory M1 phenotype, highlighting NOX2 as a potential target for novel neuroprotective therapies in glaucoma management.

Long non-coding RNAs (lncRNAs) participate in acute lung injury (ALI). However, their latent biological function and molecular mechanism have not been fully understood. In the present study, the global expression profiles of lncRNAs and mRNAs between the control and lipopolysaccharide (LPS)-stimulated groups of human normal lung epithelial cells (BEAS-2B) were determined using high-throughput sequencing. Overall, a total of 433 lncRNAs and 183 mRNAs were differentially expressed. A lncRNA–mRNA co-expression network was established, and then the top 10 lncRNAs were screened using topological methods. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis results showed that the key lncRNAs targeting mRNAs were mostly enriched in the inflammatory-related biological processes. Gene set variation analysis and Pearson’s correlation coefficients confirmed the close correlation for the top 10 lncRNAs with inflammatory responses. A protein–protein interaction network analysis was conducted based on the key lncRNAs targeting mRNAs, where IL-1β, IL-6, and CXCL8 were regarded as the hub genes. A competing endogenous RNA (ceRNA) modulatory network was created with five lncRNAs, thirteen microRNAs, and twelve mRNAs. Finally, real-time quantitative reverse transcription-polymerase chain reaction was employed to verify the expression levels of several key lncRNAs in BEAS-2B cells and human serum samples.

Notch pathway has played a significant role in the pathophysiology of pulmonary hypertension (PH). However, the role of Jagged 2 (Jag2), one ligand of Notch, remains to be elucidated.Therefore, determining the contribution of Jag2 to PH and its impact on pulmonary artery smooth muscle cells (PASMCs) was the aim of this investigation. Adeno-associated virus-mediated Jag2 inhibition was used to explore the role of Jag2 in peripheral pulmonary vascular remodeling assessed in a rat model of chronic hypoxia (10% O2, 4 weeks) induced pulmonary hypertension. In vitro, the effect of Jag2 silencing on hypoxia (1% O2, 24h) induced rat PASMCs was determined. Group differences were assessed using a 2-sided unpaired Student's t-test for two groups and one-way ANOVA for multiple groups. Jag2 upregulation was first confirmed in rats with sustained hypoxia-induced PH using publicly available gene expression data, experimental PH rat models and hypoxia induced rat PASMCs. Jag2 deficiency decreased oxidative stress injury, peripheral pulmonary vascular remodeling (0.276±0.020 vs. 0.451±0.033 μm, P

Abstract The cGAS‐STING pathway, as a vital innate immune signaling pathway, has attracted considerable attention in tumor immunotherapy research. However, STING agonists are generally incapable of targeting tumors, thus limiting their clinical applications. Here, a photodynamic polymer (P1) is designed to electrostatically couple with 56MESS–a cationic platinum (II) agent–to form NPPDT‐56MESS. The accumulation of NPPDT‐56MESS in the tumors increases the efficacy and decreases the systemic toxicity of the drugs. Moreover, NPPDT‐56MESS generates reactive oxygen species (ROS) under the excitation with an 808 nm laser, which then results in the disintegration of NPPDT‐56MESS. Indeed, the ROS and 56MESS act synergistically to damage DNA and mitochondria, leading to a surge of cytoplasmic double‐stranded DNA (dsDNA). This way, the cGAS‐STING pathway is activated to induce anti‐tumor immune responses and ultimately enhance anti‐cancer activity. Additionally, the administration of NPPDT‐56MESS to mice induces an immune memory effect, thus improving the survival rate of mice. Collectively, these findings indicate that NPPDT‐56MESS functions as a chemotherapeutic agent and cGAS‐STING pathway agonist, representing a combination chemotherapy and immunotherapy strategy that provides novel modalities for the treatment of uveal melanoma.

Purpose: In this study, we aim to investigate the potential of nintedanib as a therapeutic approach to proliferative vitreoretinopathy (PVR), which is the leading cause of failure in retinal detachment repair. PVR is characterized by the epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells, and understanding the effects of nintedanib on EMT in the normal human vitreous (HV)-induced RPE cells is crucial. Methods: Our research focuses on assessing the impact of nintedanib on HV-induced EMT in human retinal pigment epithelial (ARPE-19) cells in vitro. We employed various techniques, including quantitative real-time PCR (qPCR), western blot analysis, and immunofluorescence staining, to evaluate the mRNA and protein expression of EMT biomarkers in HV-induced ARPE-19 cells. Additionally, we measured the proliferation of RPE cells using cell counting, CCK-8, and Ki-67 assays. Migration was assessed through wound healing and transwell migration assays, while contraction was determined using a collagen gel contraction assay. Morphological changes were examined using phase-contrast microscopy. Results: Our results demonstrate that nintedanib selectively attenuates the upregulation of mesenchymal markers in HV-induced ARPE-19 cells, at both the mRNA and protein levels. Furthermore, nintedanib effectively suppresses the HV-induced proliferation, migration, and contraction of ARPE-19 cells, while maintaining the cells' basal activity. These findings strongly suggest that nintedanib exhibits protective effects against EMT in ARPE-19 cells and could be a promising therapeutic option for PVR. Conclusions: By elucidating the anti-EMT effects of nintedanib in HV-induced RPE cells, our study highlights the potential of this oral triple tyrosine kinase inhibitor in the treatment of PVR. These findings contribute to the growing body of research aimed at developing novel strategies to prevent and manage PVR, ultimately improving the success rates of retinal detachment repair.

Background: Although the current role of cytokines and neuroinflammation in glaucoma remains obscure, it represents an expanding field in research. The purpose of this study was to analyze cytokines in the aqueous humor (AH) of glaucoma patients and in retinas from an ex vivo glaucoma animal model, to aid in determining the role of neuroinflammation in glaucoma. Methods: AH samples were collected from 20 patients during cataract surgeries (controls: n = 10, age = 70.3 ± 9.742; glaucoma: n = 10, age: 66.5 ± 8.073) in Shanghai East Hospital, an affiliate of Tongji University, between September 2018 and March 2019 and analyzed in duplicate by Luminex cytokine polystyrene color bead-based multiplex assay. Retinas from female Sprague-Dawley rats (n = 6) were harvested ex vivo and cultured with or without 60 mmHg of hydrostatic pressure for 24 hours. Retinal ganglion cells (RGCs) were quantified using Brn3a staining. Cytokines in the retina and culture medium were analyzed by rat cytokine array (Abcam). Results: At baseline, patients with primary angle closure glaucoma (PACG) have significantly lower levels of IL-6 and IP-10 and a higher level of PDGF-BB in their AH, compared to the controls. Postoperatively, patients with PACG have significantly higher levels of IL-1ra, IL-13, and MIP-1α and a lower level of IL-6. Elevated hydrostatic pressure led to significant RGC loss in the retina, ex vivo, as well as the upregulation of ciliary neurotrophic factor (CNTF), IL-6, IL-10, IL-4, and TIMP-1 alongside the downregulation of PDGF-AA, MMP-8, TNF-α, and IFN-γ. Furthermore, eight cytokines were detected as being downregulated in the culture medium, including PDGF-AA, MMP-8, and IL-4. Conclusions: Proinflammatory cytokines showed changes in both AH and ex vivo. Further studies are needed on the role of these cytokines and their corresponding signaling pathways in both neurodegeneration and glaucoma.

Epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is a key fibrosis pathogenesis in proliferative vitreoretinopathy (PVR). However, few medicines can prevent proliferative membranes and cell proliferation in the clinic. Nintedanib, a tyrosine kinase inhibitor, has been shown to prevent fibrosis and be anti-inflammatory in multiple organ fibrosis. In our study, 0.1, 1, 10 μM nintedanib was added to 20 ng/mL transforming growth factor beta 2 (TGF-β2)-induced EMT in ARPE-19 cells. Western blot and immunofluorescence assay showed that 1 μM nintedanib suppressed TGF-β2-induced E-cadherin expression decreased and Fibronectin, N-cadherin, Vimentin, and α-SMA expression increased. Quantitative real-time PCR results showed that 1 μM nintedanib decreased TGF-β2-induced increase in SNAI1, Vimentin, and Fibronectin expression and increased TGF-β2-induced decrease in E-cadherin expression. In addition, the CCK-8 assay, wound healing assay, and collagen gel contraction assay also showed that 1 μM nintedanib ameliorated TGF-β2-induced cell proliferation, migration, and contraction, respectively. These results suggested that nintedanib inhibits TGF-β2-induced EMT in ARPE-19 cells, which may be a potential pharmacological treatment for PVR.

PurposeGlaucoma is a leading cause of irreversible blindness worldwide. Retinal ganglion cells (RGC), the neurons that connect the eyes to the brain, specifically die in glaucoma, leading to blindness. Elevated intraocular pressure (IOP) is the only modifiable risk factor, however, many patients progress despite excellent IOP control. Thus, alternative treatment strategies to prevent glaucoma progression are an unmet need. Citicoline has demonstrated neuroprotective properties in central neurodegenerative diseases. However, conclusive evidence of the effect of citicoline on glaucoma progression is missing. This systematic review investigates first-time the therapeutic potential of citicoline in glaucoma patients.MethodsThe present study was conducted according to the PRISMA 2020 statement. PubMed, Web of Science, Google Scholar, and Embase were accessed in July 2023 to identify all clinical studies investigating the efficacy of citicoline on IOP, the mean deviation of the 24-2 visual field testing (MD 24-2), retinal nerve fibre layer (RNFL), and the pattern electroretinogram (PERG) P50-N95 amplitude in glaucoma patients. The risk of bias was assessed using the Review Manager 5.3 software (The Nordic Cochrane Collaboration, Copenhagen) and the Risk of Bias in Non-randomised Studies of Interventions (ROBINS-I) tool.ResultsTen studies were eligible for this systematic review, including 424 patients. The mean length of the follow-up was 12.1 ± 11.6 months. The overall risk of bias was low to moderate. The mean age of the patients was 56.7 years. There were no significant differences in the IOP, MD 24-2, RNFL, or PERG P50-N95 amplitude between patients receiving citicoline and the control group. There was no improvement from baseline to the last follow-up in IOP, MD 24-2, RNFL, or PERG P50-N95 amplitude.ConclusionThere is a lack of sufficient evidence to support that citicoline slows the progression of glaucoma.

AIM: To unravel the primary open angle glaucoma (POAG) related proteomic changes in aqueous humour (AH). METHODS: Totally 35 patients listed for cataract surgery (controls: n=12, age: 67.4±13.6y) or trabeculectomy for POAG (n=23, age: 72.5±8.3y) were included. AH samples of those patients were obtained during cataract surgery or trabeculectomy. AH samples were subsequently pooled into the experimental groups under equal contribution in terms of protein amount of each individual patient. Protein samples were analyzed by a linear trap quadrupol Orbitrap Mass Spectrometry device with an upstream liquid chromatography system. The obtained raw data were analyzed using the Maxquant proteome software and compared. Proteins with a fold-change ratio higher than a cut-off of 2 were considered as noticeably altered. RESULTS: A total number of 175 proteins could be identified out of the AH from POAG and cataract by means of quantitative mass spectrometric analysis. Apolipoprotein D (fold change, 3.16 times), complement C3 (2.96), pigment epithelium-derived factor (2.86), dickkopf-related protein 3 (2.18) and wingless-related integration (Wnt) inhibitory factor 1 (2.35) were significantly upregulated within the AH of glaucoma compared to cataract serving as controls. CONCLUSION: AH provides a tool to analyze changes in glaucoma and shows striking changes in Wnt signaling inhibitory molecules and other proteins.

The relative pose estimation of the space target is indispensable for on-orbit autonomous service missions. Line segment detection is an important step in pose estimation. The traditional line segment detectors show impressive performance under sufficient illumination, while it is easy to fail under complex illumination conditions where the illumination is too bright or too dark. We propose a robust line segment detector for space applications considering the complex illumination in space environments. An improved two-dimensional histogram construction strategy is used to optimize the Otsu method to improve the accuracy of anchor map extraction. To further improve line segment detection’s effect, we introduce an aggregation method that uses the angle difference between segments, the distance between endpoints, and the overlap degree of segments to filter the aggregation candidate segments and connect disjoint line segments that probably came from the same segment. We demonstrate the performance of the proposed line segment detector using a variety of images collected on a semiphysical simulation platform. The results show that our method has better performance than traditional line segment detectors including LSD, Linelet, etc., in terms of line detection precision.

Protein–small molecule interactions naturally occur in foodstuffs, which could improve the properties of protein and small molecules. Meanwhile, they might affect the bioavailability and nutritional value of proteins. Ferritin, as an iron-storage protein, has been a focus of research. However, the complexity of foodstuffs enables the interaction between ferritin and food components, especially polyphenols, which can induce iron release from ferritin. Thus, the application of ferritin in food is limited. Inspired by the natural-occurring, strong protein–polyphenol interactions in beer, to inhibit the iron release of ferritin, the malt-derived protein Z (PZ) was chosen to interact with ferulic acid (FA), an abundant reductant in malt, beer, and other foodstuffs. The analysis of the interaction between PZ and FA was carried out using fluorescence spectroscopy, the results of which suggest that one PZ molecule can bind with 22.11 ± 2.13 of FA, and the binding constant is (4.99 ± 2.13) × 105 M−1. In a molecular dynamics (MD) simulation, FA was found to be embedded in the internal hydrophobic pocket of PZ, where it formed hydrogen bonds with Val-389 and Tyr-234. As expected, compared to iron release induced by FA, the iron release from donkey spleen ferritin (DSF) induced by FA decreased by 86.20% in the presence of PZ. Meanwhile, based on the PZ–FA interaction, adding PZ in beer reduced iron release from DSF by 40.5% when DSF:PZ was 1:40 (molar ratio). This work will provide a novel method of inhibiting iron release from ferritin.

Gout is one of the most prevalent rheumatic diseases, globally. Colchicine (COL) is the first-line drug used for the treatment of acute gout. However, the oral administration of COL is restricted, owing to serious adverse reactions. Therefore, this study aimed to develop a drug-in-adhesive (DIA) patch to achieve transdermal delivery of COL. We investigated the solubility of COL in different pressure-sensitive adhesives (PSAs) using slide crystallization studies. The COL-DIA patches were optimized based on in vitro skin penetration studies and evaluated by in vivo pharmacokinetics and pharmacodynamics. The results showed that the optimized COL-DIA patch contained 10% COL, Duro-Tak 87-2516 as PSA, 5% oleic acid (OA) and 5% propylene glycol (PG) as permeation enhancer, exhibiting the highest in vitro cumulative penetration amount of COL (235.14 ± 14.47 μg∙cm−2 over 48 h). Pharmacokinetic studies demonstrated that the maximum plasma drug concentration (Cmax) was 2.65 ± 0.26 ng/L and the mean retention time (MRT) was 37.47 ± 7.64 h of the COL-DIA patch, effectively reducing the drug side effects and prolonging drug activity. In addition, pharmacodynamic studies showed the patch significantly decreased the expression levels of inflammatory factors of gouty rats and reduced pathological damage in the ankle joint of rats, making it an attractive alternative to the administration of COL for the treatment of gout.

Research has been conducted into vascular abnormalities in the pathogenesis of glaucoma, but conclusions remain controversial. Our aim was to test the hypothesis that retinal endothelial dysfunction induced by elevated intraocular pressure (IOP) persists after IOP normalization, further triggering retinal ganglion cell (RGC) loss. High intraocular pressure (HP) was induced in mice by episcleral vein occlusion (EVO). Retinal vascular function was measured via video microscopy in vitro. The IOP, RGC and their axons survival, levels of oxidative stress and inflammation as well as vascular pericytes coverage, were determined. EVO caused HP for two weeks, which returned to baseline afterwards. Mice with HP exhibited endothelial dysfunction in retinal arterioles, reduced density of RGC and their axons, and loss of pericytes in retinal arterioles. Notably, these values were similar to those of mice with recovered IOP (RP). Levels of oxidative stress and inflammation were increased in HP mice but went back to normal in the RP mice. Our data demonstrate that HP induces persistent endothelial dysfunction in retinal arterioles, which persists one month after RP. Oxidative stress, inflammation, and loss of pericytes appear to be involved in triggering vascular functional deficits. Our data also suggest that retinal endothelial dysfunction does not affect RGC and their axon survival.

Background: Bilateral sequential cataract surgery within a short period is becoming more prevalent because of the efficiency and safety of modern cataract surgery. It has been reported that the first surgical eye might affect the contralateral eye. This study investigated the cytokines involved in the immunopathogenesis of pre-existing ocular or systemic conditions, as well as the inflammatory biomarkers in response to topical stimuli, by analyzing the cytokine profile of aqueous humor (AH) from cataract patients without these morbidities as control and with type 2 diabetes mellitus (DM), primary angle-closure glaucoma (PACG) or high myopia (HM) in each eye at the beginning of first (defined as baseline) and second eye cataract surgery. Methods: Forty patients were recruited in this cohort study (10/group). Bilateral sequential cataract surgeries were conducted at intervals of 12.08 ± 1.2 days. Aqueous humor samples (100–200 μL/eye) were separately collected from 40 first-eyes and 40 second-eyes at the beginning of the cataract surgeries. Twenty-seven selected cytokines were detected with Luminex-multiplex immunoassay. The concentrations of cytokines in the aqueous humor and their association with pre-existing ocular or systemic conditions were analyzed and compared between and within the groups. Results: Before first-eye surgery (baseline), the levels of interleukin (IL)-1ra, IL-13 and tumor necrosis factor (TNF)-alpha were significantly increased in PACG compared with controls. The levels of IL-13 were increased while that of IL-15 were decreased in HM. Compared with controls, 11 cytokines were significantly increased in DM. In the AH of the contralateral eye after first-eye cataract surgery, basic fibroblast growth factor (bFGF) was significantly more abundant in PACG and HM, while the levels of monocyte chemoattractant protein-1 (MCP-1) and interferon gamma-induced protein 10 (IP-10) were decreased in PACG. We also identified 6 significantly upregulated cytokines in DM compared with controls. Compared with baseline, there was an overlap of 5 altered cytokines in the AH of contralateral eyes after first-eye surgery between the four groups. Some were exclusively altered in each subgroup, with 1 in the control group, 4 cytokines in the PACG and HM groups, and none in the DM group. Conclusions: From the initial profile, it is observed that patients with pre-existing ocular or systemic conditions have some degree of inflammation in their eyes before surgery and in the contralateral eye after the first eye cataract surgery, which could be peculiar of the morbid conditions of the patients. Inflammation was more detectable in patients with type 2 DM before surgery. PACG and HM patients showed stronger intraocular inflammatory reactions to topical stimuli compared with controls and DM patients. Our data suggest that ophthalmologists should pay closer attention to inflammatory responses, especially in cataract patients with pre-existing conditions, although the clinical significance of these changes following surgery remains to be further investigated.

Oxidative stress (OS) is an imbalance between free radicals/ROS and antioxidants, which evokes a biological response and is an important risk factor for diseases, in both the cardiovascular system and central nervous system (CNS). The underlying mechanisms driving pathophysiological complications that arise from OS remain largely unclear. The vascular endothelium is emerging as a primary target of excessive glucocorticoid and catecholamine action. Endothelial dysfunction (ED) has been implicated to play a crucial role in the development of neurodegeneration in the CNS. The retina is known as an extension of the CNS. Stress and endothelium dysfunction are suspected to be interlinked and associated with neurodegenerative diseases in the retina as well. In this narrative review, we explore the role of OS-led ED in the retina by focusing on mechanistic links between OS and ED, ED in the pathophysiology of different retinal neurodegenerative conditions, and how a better understanding of the role of endothelial function could lead to new therapeutic approaches for neurodegenerative diseases in the retina.

Purpose. Glaucoma, one of the leading causes of irreversible blindness worldwide, is a group of disorders characterized by progressive retinal ganglion cell (RGC) loss. Synucleins, a family of small proteins, have been of interest in studies of neurodegeneration and CNS. However, their roles and functions in glaucoma are still not completely understood and remain to be explored. Our previous studies showed that α-synuclein and H2S play a pivotal role in glaucoma. This study aims to (1) elucidate the potential roles and functions of synucleins in glaucoma throughout aging, (2) investigate the interaction between the synucleins and H2S, and better understand the mechanism of H2S in neuroprotection. Methods. The chronic IOP elevation model was carried out in 12 animals at different ages (3 months and 14 months), and RGCs were quantified by Brn3a staining. Mass spectrometric-assisted proteomics analysis was employed to measure synuclein levels and H2S producing proteins in retina. Secondly, the acute IOP elevation model was carried out in 12 juvenile animals, with or without intravitreal injection of GYY4137 (a H2S donor). RGCs were quantified along with the abundancy of synucleins. Results. RGCs and β-synuclein (SNCB) are significantly changed in old animals. Under chronic IOP elevation, there is a significant RGC loss in old animals, whereas no significant change in young animals; SNCB is significantly downregulated and 3MST is significantly upregulated in young animals due to IOP, while no significant changes in old ones are notable. Under acute IOP elevation (approx. 55 mmHg), a significant RGC loss is observed; exogenous H2S significantly reduced RGC loss and downregulated SNCB levels. Conclusion. The present study indicates a strong link between ageing and SNCB regulation. In young animals SNCB is downregulated going along with less RGC loss. Furthermore, increasing endogenous H2S is effective to downregulate SNCB and is neuroprotective against acute IOP elevation.

Mitochondria are the energy factories of cells. Mitochondrial dysfunction directly affects the function and morphology of cells. In recent years, growing evidence has shown that mitochondrial dysfunction plays an important role in neurodegenerative diseases. In the eye, some age-related diseases are considered to be neurodegenerative diseases, such as primary open-angle glaucoma (POAG) and age-related macular degeneration (AMD). Here, we review the mechanisms of mitochondrial damage, post-injury repair, and the roles of mitochondria in various tissues of the eye. In the following sections, the potential for treating glaucoma by reducing mitochondrial damage and promoting post-injury repair is also discussed.

PurposeTo analyze the potential neuro-protective and neuro-regenerative effects of Collapsin-response-mediator-protein-5 (CRMP-5) on retinal ganglion cells (RGCs) using in vitro and in vivo animal models of glaucoma.MethodsElevated intraocular pressure (IOP) was induced in adult female Sprague-Dawley (SD) rats by cauterization of three episcleral veins. Changes in CRMP-5 expression within the retinal proteome were analyzed via label-free mass spectrometry. In vitro, retinal explants were cultured under elevated pressure (60 mmHg) within a high-pressure incubation chamber with and without addition of different concentrations of CRMP-5 (4 μg/l, 200 μg/l and 400 μg/l). In addition, retinal explants were cultured under regenerative conditions with and without application of 200 μg/l CRMP-5 after performing an optic nerve crush (ONC). Thirdly, an antibody against Protein Kinase B (PKB) was added to examine the possible effects of CRMP-5. RGC count was performed. Number and length of the axons were determined and compared. To undermine a signal-transduction pathway via CRMP-5 and PKB microarray and immunohistochemistry were performed.ResultsCRMP-5 was downregulated threefold in animals showing chronically elevated IOP. The addition of CRMP-5 to retinal culture significantly increased RGC numbers under pressure in a dose-dependent manner and increased and elongated outgrowing axons in retinal explants significantly which could be blocked by PKB. Especially the number of neurites longer than 400 μm significantly increased after application of CRMP-5. CRMP-5 as well as PKB were detected higher in the experimental than in the control group.ConclusionCRMP-5 seems to play an important role in an animal model of glaucoma. Addition of CRMP-5 exerts neuro-protective and neuro-regenerative effects in vitro. This effect could be mediated via activation of PKB affecting intra-cellular apoptosis pathways.

Oxidative stress (OS) damage can cause significant injury to cells, which is related to the occurrence and development of many diseases. This pathological process is considered to be the first step to trigger the death of outer retinal neurons, which is related to the pathology of retinal degenerative diseases. Hydrogen sulfide (H2S) has recently received widespread attention as a physiological signal molecule and gas neuromodulator and plays an important role in regulating OS in eyes. In this article, we reviewed the OS responses and regulatory mechanisms of H2S and its donors as endogenous and exogenous regulators in retinal degenerative diseases. Understanding the relevant mechanisms will help to identify the therapeutic potential of H2S in retinal degenerative diseases.

Glaucoma is a group of diseases characterized by the progressive loss of retinal ganglion cells and their axons. Elevated intraocular pressure (IOP) is the main clinical manifestation of glaucoma. Despite being in the focus of the studies for decades, the characteristic and the exact pathology of neurodegeneration in glaucoma remains unclear. Oxidative stress is believed to be one of the main risk factors in neurodegeneration, especially its damage to the retinal ganglion cells. Hydrogen sulfide (H2S), the recently recognized gas signaling molecule, plays a pivotal role in the nervous system, vascular system, and immune system. It has also shown properties in regulating oxidative stress through different pathways in vivo. In this review, we summarize the distribution and the properties of H2S within the eye with an emphasis on its role in modulating oxidative stress in glaucoma.

Both intrinsic and external signals regulate stem cell fate. Here, the authors perform a genome-wide RNAi screen to identify regulators of testis germline stem cells (GSC) in Drosophila, finding more than half of the genes were external regulators and heterochromatin/cytokinesis proteins mediated GSC fate.

Glaucoma is the leading cause of irreversible blindness and is characterized by progressive retinal ganglion cell (RGC) degeneration. Hydrogen sulfide (H2S) is a potent neurotransmitter and has been proven to protect RGCs against glaucomatous injury in vitro and in vivo. This study is to provide an overall insight of H2S’s role in glaucoma pathophysiology. Ischemia-reperfusion injury (I/R) was induced in Sprague-Dawley rats (n = 12) by elevating intraocular pressure to 55 mmHg for 60 min. Six of the animals received intravitreal injection of H2S precursor prior to the procedure and the retina was harvested 24 h later. Contralateral eyes were assigned as control. RGCs were quantified and compared within the groups. Retinal proteins were analyzed via label-free mass spectrometry based quantitative proteomics approach. The pathways of the differentially expressed proteins were identified by ingenuity pathway analysis (IPA). H2S significantly improved RGC survival against I/R in vivo (p < 0.001). In total 1115 proteins were identified, 18 key proteins were significantly differentially expressed due to I/R and restored by H2S. Another 11 proteins were differentially expressed following H2S. IPA revealed a significant H2S-mediated activation of pathways related to mitochondrial function, iron homeostasis and vasodilation. This study provides first evidence of the complex role that H2S plays in protecting RGC against I/R.

The intestinal epithelium is the most rapidly self-renewing tissue in adult animals and maintained by intestinal stem cells (ISCs) in both Drosophila and mammals. To comprehensively identify genes and pathways that regulate ISC fates, we performed a genome-wide transgenic RNAi screen in adult Drosophila intestine and identified 405 genes that regulate ISC maintenance and lineage-specific differentiation. By integrating these genes into publicly available interaction databases, we further developed functional networks that regulate ISC self-renewal, ISC proliferation, ISC maintenance of diploid status, ISC survival, ISC-to-enterocyte (EC) lineage differentiation, and ISC-to-enteroendocrine (EE) lineage differentiation. By comparing regulators among ISCs, female germline stem cells, and neural stem cells, we found that factors related to basic stem cell cellular processes are commonly required in all stem cells, and stem-cell-specific, niche-related signals are required only in the unique stem cell type. Our findings provide valuable insights into stem cell maintenance and lineage-specific differentiation.

We conducted a meta-analysis of published retrospective studies and compared the effectiveness of pars plana vitrectomy with and without internal limiting membrane (ILM) peeling for idiopathic epiretinal membrane (IERM). The results revealed that patients in the IERM+ILM peeling group had better BCVA after surgery within 12 months than those in IERM peeling group. But patients in the IERM peeling group showed better BCVA in the 18th month. More retrospective studies or randomized controlled trials are required to investigate and compare the long-term effect of IERM removal with and without ILM peeling.

Phosphorus deficiency limits plant growth and development. To better understand the mechanisms behind how maize responds to phosphate stress, we compared the proteome analysis results of two groups of maize leaves that were treated separately with 1,000 µM (control, +P) and 5 µM of KH2PO4 (intervention group, -P) for 25 days. In total, 1,342 protein spots were detected on 2-DE maps and 15.43% had changed (P