Role of mRNA-binding proteins in retinal neovascularization.

Retinal neovascularization (RNV) is a pathological process that primarily occurs in diabetic retinopathy, retinopathy of prematurity, and retinal vein occlusion. It is a common yet debilitating clinical condition that culminates in blindness. Urgent efforts are required to explore more efficient and less limiting therapeutic strategies. Key RNA-binding proteins (RBPs), crucial for post-transcriptional regulation of gene expression by binding to RNAs, are closely correlated with RNV development. RBP-RNA interactions are altered during RNV. Here, we briefly review the characteristics and functions of RBPs, and the mechanism of RNV. Then, we present insights into the role of the regulatory network of RBPs in RNV. HuR, eIF4E, LIN28B, SRSF1, METTL3, YTHDF1, Gal-1, HIWI1, and ZFR accelerate RNV progression, whereas YTHDF2 and hnRNPA2B1 hinder it. The mechanisms elucidated in this review provide a reference to guide the design of therapeutic strategies to reverse abnormal processes.

Examining the etiological factors resulting in retinal detachment following prophylactic vitrectomy in the context of acute retinal necrosis syndrome.

OBJECTIVE: The aim of this study is to elucidate the factors contributing to the occurrence of retinal detachment (RD) following prophylactic vitrectomy in cases of acute retinal necrosis (ARN) syndrome. METHODS: A retrospective examination was undertaken, encompassing the medical records of patients diagnosed with ARN who underwent prophylactic vitreous intervention at the Ophthalmology Department of Wuhan University Renmin Hospital East Campus between October 2019 and September 2023. Subsequently, patients who manifested RD in the postoperative period were identified, and a comprehensive analysis was conducted to ascertain the factors underlying the occurrence of RD post-surgery. RESULTS: This study comprised 14 cases (involving 14 eyes) of patients diagnosed with ARN who underwent prophylactic vitreous intervention. The findings revealed that 4 patients experienced postoperative RD, resulting in an incidence rate of 28.57%. Notably, among these cases, 3 cases of RD manifested in the presence of silicone oil, while 1 case occurred subsequent to the removal of silicone oil. All 4 cases of RD exhibited varied degrees of proliferative vitreoretinopathy. Following the occurrence of RD, all patients underwent a secondary vitreous intervention coupled with silicone oil tamponade, leading to successful reattachment of the retina. However, despite these interventions, there was no significant enhancement observed in postoperative visual outcomes when compared to preoperative levels. CONCLUSION: RD following prophylactic vitrectomy in cases of ARN is not an infrequent occurrence and is primarily linked to the postoperative onset of proliferative vitreoretinopathy.

A controlled clinical study on efficacy and safety of periocular triamcinolone acetonide injection for treating ocular myasthenia gravis.

OBJECTIVE: To evaluate the efficacy and safety of peribulbar triamcinolone acetonide injection for treating ocular myasthenia gravis (OMG), with a comparison of traditional oral drug therapy. METHODS: A total of 22 patients with OMG who received periocular triamcinolone acetonide injection (initially 20 mg weekly, then once per month later if symptoms were improved) from July 2019 to July 2022 were evaluated by a comparison of symptom degree before and after treatment. Adverse reactions were also monitored during the period of treatment. The period of follow-up was more than 6 months. Additionally, a comparison of the treatment efficacy between this periocular injection and traditional oral administration was performed in OMG patients. RESULTS: After 4 weeks of treatment, the degree of ptosis in OMG patients decreased to -3.00 ± 0.69, compared to the value (-0.86 ± 1.32) before treatment. The degree of ophthalmoplegia also decreased from 3.12 ± 0.72 to 0.86 ± 0.88 (P < 0.001) after treatment. The achievement rates of minimal manifestations status (MMS)for ptosis and ophthalmoplegia after 4 week-treatment were 86.3% and 75%, respectively, while they were 50% and 30% in patients with traditional oral administration. There was statistically significant difference only in MMS (rather than symptom relief rate and generalization conversion rate) between two groups. No serious complications (except for intraorbital hematoma) were found in OMG patients during the treatment period. CONCLUSION: Repeated peribulbar injection of triamcinolone acetonide can effectively alleviate the initial symptoms of OMG patients. However, the evaluation of its long-term efficacy is still needed. CLINICAL TRIAL REGISTRY: This study has been clinically registered by Chinese Clinical Trial Registry (ChiCTR), first trial registration date:05/07/2019, registration number: ChiCTR1900024285.

Galectin-1-dependent ceRNA network in HRMECs revealed its association with retinal neovascularization.

BACKGROUND: Retinal neovascularization (RNV) is a leading cause of blindness worldwide. Long non-coding RNA (lncRNA) and competing endogenous RNA (ceRNA) regulatory networks play vital roles in angiogenesis. The RNA-binding protein galectin-1 (Gal-1) participates in pathological RNV in oxygen-induced retinopathy mouse models. However, the molecular associations between Gal-1 and lncRNAs remain unclear. Herein, we aimed to explore the potential mechanism of action of Gal-1 as an RNA-binding protein. RESULTS: A comprehensive network of Gal-1, ceRNAs, and neovascularization-related genes was constructed based on transcriptome chip data and bioinformatics analysis of human retinal microvascular endothelial cells (HRMECs). We also conducted functional enrichment and pathway enrichment analyses. Fourteen lncRNAs, twenty-nine miRNAs, and eleven differentially expressed angiogenic genes were included in the Gal-1/ceRNA network. Additionally, the expression of six lncRNAs and eleven differentially expressed angiogenic genes were validated by qPCR in HRMECs with or without siLGALS1. Several hub genes, such as NRIR, ZFPM2-AS1, LINC0121, apelin, claudin-5, and C-X-C motif chemokine ligand 10, were found to potentially interact with Gal-1 via the ceRNA axis. Furthermore, Gal-1 may be involved in regulating biological processes related to chemotaxis, chemokine-mediated signaling, the immune response, and the inflammatory response. CONCLUSIONS: The Gal-1/ceRNA axis identified in this study may play a vital role in RNV. This study provides a foundation for the continued exploration of therapeutic targets and biomarkers associated with RNV.

COG1410 regulates microglial states and protects retinal ganglion cells in retinal ischemia-reperfusion injury.

Progressive loss of retinal ganglion cells (RGCs) caused by retinal ischemia-reperfusion (IR) injury can lead to irreversible vision impairment, with neuroinflammatory responses playing an important role in this process. COG1410, a mimetic peptide of apolipoprotein E, has demonstrated protective potential in the central nervous system, but its effects on retinal IR injury remain unexplored. In this study, we established a mouse model of retinal IR injury to investigate the effects of COG1410 on retinal microglia and RGCs. We observed CD16/32-marked and CD206-marked microglia and RGCs using immunofluorescence staining, detected the expression of inflammatory factors by PCR, and evaluated retinal apoptosis with TUNEL staining. We further investigated the potential mechanism by detecting the expression of key proteins via Western blot. The results reveal that COG1410 decreased the number of CD16/32-marked microglia and increased the number of CD206-marked microglia, alleviated the expression of IL-1ß and TNF-α, and reduced the loss of RGCs by inhibiting the mitochondrial-related apoptotic pathway. COG1410 was found to increase the expression of ERK1/2 and Nr4a1 but decrease the expression of NF-κB. The expression of TREM2 showed an increasing trend after COG1410 administration, but it was not statistically significant. In conclusion, COG1410 regulates microglial states and protects RGCs in retinal IR injury, showing promising potential for the treatment of eye diseases.

Long Non-Coding RNAs in Retinal Ganglion Cell Apoptosis.

Traumatic optic neuropathy or other neurodegenerative diseases, including optic nerve transection, glaucoma, and diabetic retinopathy, can lead to progressive and irreversible visual damage. Long non-coding RNAs (lncRNAs), which belong to the family of non-protein-coding transcripts, have been linked to the pathogenesis, progression, and prognosis of these lesions. Retinal ganglion cells (RGCs) are critical for the transmission of visual information to the brain, damage to which results in visual loss. Apoptosis has been identified as one of the most essential modes of RGC death. Emerging evidence suggests that lncRNAs can regulate RGC degeneration by directly or indirectly modulating apoptosis-associated signaling pathways. This review presents a comprehensive overview of the role of lncRNAs in RGC apoptosis at transcriptional, post-transcriptional, translational, and post-translational levels, emphasizing on the potential mechanisms of action. The current limitations and future perspectives of exploring the connection between lncRNAs and RGC apoptosis have been summarized. Understanding the intricate molecular interaction network of lncRNAs and RGC apoptosis will open new avenues for the identification of novel diagnostic biomarkers, therapeutic targets, and molecules for prognostic evaluation of diseases related to RGC injury.

Park7 protects retinal ganglion cells and promotes functional preservation after optic nerve crush via regulation of the Nrf2 signaling pathway.

PURPOSE: We aim to investigate the effect of Park7 on mice RGC survival and function following optic nerve crush (ONC), and to explore its potential mechanism. METHODS: Wild-type male C57BL/6J mice were subjected to optic nerve crush. Six weeks before ONC, mice received rAAV-shRNA (Park7)-EGFP or rAAV-EGFP intravitreally. Western blotting was used to detect Park7 levels. RGC survival was measured using immunofluorescence. Retinal cell apoptosis was detected using terminal deoxynucleotidyl transferase nick-end-labelling. An electroretinogram (ERG) and the optomotor response (OMR) were used to assess RGC function. Kelch-like ECH-associated protein 1 (Keap1), nuclear factor erythroid 2-related factor (Nrf2), and heme oxygenase 1 (HO-1) levels were assessed using western blotting. RESULTS: ONC injury increased the relative expression of Park7 significantly and decreased RGC survival, the amplitude of the photopic negative response (PhNR), and OMR. Intravitreal injection of rAAV-shRNA(Park7)-EGFP downregulated Park7 expression and was clearly demonstrated by the green fluorescence protein in many retinal layers. Moreover, Park7 downregulation aggravated the decrease in RGC survival and amplitude of PhNR as well as the visual acuity after ONC. However, inhibition of Park7 significantly increased Keap1 levels, decreased the total and nuclear Nrf2 levels, and reduced HO-1 levels. CONCLUSIONS: Park7 downregulation enhanced RGC injury and decreased retinal electrophysiological response and OMR after ONC in mice via the Keap1-Nrf2-HO-1 signaling pathway. Park7 may have neuroprotective effects and could represent a novel way to treat optic neuropathy.

Long non-coding RNAs in retinal neovascularization: current research and future directions.

PURPOSE: Retinal neovascularization (RNV) is an intractable pathological hallmark of numerous ocular blinding diseases, including diabetic retinopathy, retinal vein occlusion, and retinopathy of prematurity. However, current therapeutic methods have potential side effects and limited efficacy. Thus, further studies on the pathogenesis of RNV-related disorders and novel therapeutic targets are critically required. Long non-coding RNAs (lncRNAs) have various functions and participate in almost all biological processes in living cells, such as translation, transcription, signal transduction, and cell cycle control. In addition, recent research has demonstrated critical modulatory roles of various lncRNAs in RNV. In this review, we summarize current knowledge about the expression and regulatory functions of lncRNAs related to the progression of pathological RNV. METHODS: We searched databases such as PubMed and Web of Science to gather and review information from the published literature. CONCLUSIONS: In general, lncRNA MEG3 attenuates RNV, thus protecting the retina from excessive and dysregulated angiogenesis under high glucose stress. In contrast, lncRNAs MALAT1, MIAT, ANRIL, HOTAIR, HOTTIP, and SNHG16, have been identified as causative molecules in the pathological progression of RNV. Comprehensive and in-depth studies of the roles of lncRNAs in RNV indicate that targeting lncRNAs may be an alternative therapeutic approach in the near future, enabling new options for attenuating RNV progression and treating RNV-related retinal diseases.

Contemplating the necessity of surgical treatment for posterior lenticonus: a case report.

BACKGROUND: Posterior lenticonus is an uncommon congenital abnormality that causes a progressive, localized spherical or conical bulging of the posterior capsular membrane, resulting in an abnormal shape of the lens. CASE PRESENTATION: A 13-year-old girl presented with ametropia in both eyes. After mydriasis, examination revealed an oval bubble-shaped alteration with a distinct boundary above the temporal region on the center of the posterior capsule of her left lens. The subcortical region surrounding the alteration appeared feathery and turbid. The patient had no history of trauma or family history of visual impairment. Systemic investigations were normal. A thorough eye examination was performed, which included optometry, ultrasound biomicroscopy, ocular B-Scan, and anterior segment optical coherence, to assess the disease. The patient was diagnosed with posterior lenticonus in the left eye, as well as ametropia and anisometropia in both eyes. Conservative treatment was initiated since the patient's current best corrected visual acuity was good, and regular monitoring of the condition's progression was scheduled. CONCLUSIONS: This case report presents a rare instance of posterior lenticonus. The findings of this report raise new considerations regarding the necessity of surgical intervention for this condition.

Clinicopathological features of corneal invasion by filtering bleb.

PURPOSE: To describe the clinicopathological characteristics and explore the possible etiology of cornea invasion by filtering bleb (CIFB) after filtering surgery. METHODS: We reviewed 22 patients treated for CIFB between March 2005 and March 2022. The patients were followed up for more than 1 year. Slit-lamp examination, optical coherence tomography (OCT), ultrasound biomicroscopy, and histopathological examination were performed to observe the morphology of the bleb and depth of corneal invasion. Depending on the severity of the lesion, treatments consisting of local massage, acupuncture separation, or surgical resection were administered. RESULTS: The mean age of the patients was 56.3 ± 8.8 years. All patients underwent filtering surgery in the moderate or advanced stage of glaucoma. The filtering bleb was closely connected with the cornea, and its posterior boundary was locally adhered. Forward displacement of the internal opening of the filtering bleb was found in 4 of 7 surgically treated patients. OCT and pathological examination showed that the filtering blebs invaded the corneal stroma. Removal of the adhesion of the posterior boundary of the filtering bleb by different treatment methods successfully improved the patients' conditions. CONCLUSION: Filtering blebs can invade the corneal stroma. Adhesion of the posterior boundary and forward displacement of the internal opening of the filtering bleb are the possible causes of CIFB. Removal of the adhesion of the posterior boundary of the filtering bleb can halt the progression of CIFB.

Construction and analysis of mRNA, lncRNA, and transcription factor regulatory networks after retinal ganglion cell injury.

Retinal ganglion cell (RGC) injury is a critical pathological feature of several optic neurodegenerative diseases. The regulatory mechanisms underlying RGC injury remain poorly understood. Recent evidence has highlighted the important roles of long noncoding RNAs (lncRNAs) in degenerative neuropathy but few studies have focused on lncRNAs associated with RGC injury. In this study, we analyzed dysregulated lncRNAs associated with RGC injury, their potential regulatory functions, and the molecular mechanisms underlying the regulation of lncRNAs and transcription factors (TFs). We analyzed lncRNA and mRNA profiles in the GSE142881 dataset associated with RGC injury and identified 1049 differentially expressed genes (DEGs), with 18 differentially expressed (DE) TFs among 883 DE mRNAs and 312 DE lncRNAs. The predicted DE lncRNAs and DE mRNAs were used to construct a lncRNA-mRNA co-expression network. Functional enrichment analysis was performed to explore the functions of the lncRNAs and mRNAs. The co-expression network between DE lncRNAs and DE mRNAs was highly enriched in inflammatory and immune-related pathways, indicating that they play role in the process of RGC injury. Among the DE mRNAs, we screened 18 DE TFs, including activating transcription factor 3 (ATF3), associated with RGC injury. Co-expression analysis predicted that 13 lncRNAs were potential binding targets of ATF3. The screening of the potential targets of these 13 lncRNAs showed that they were also significantly enriched in functional pathways associated with inflammation and apoptosis. After analysis, we constructed the mRNA-ATF3-lncRNA regulatory network after RGCs injury. In summary, we identified the gene module associated with immune and inflammatory responses after optic nerve injury and constructed a regulatory network of lncRNA-TF-mRNA. The results indicate that lncRNAs, by binding to TFs, can regulate downstream genes and function during RGC injury. The results provide a foundation for further studies of the mechanism of RGC injury and provide insight into the clinical diagnosis and investigation direction of neurodegenerative diseases such as traumatic optic neuropathy and glaucoma.

Inhibition of p66Shc attenuates retinal ischemia-reperfusion injury-induced damage by activating the akt pathway.

Retinal ganglion cell (RGC) death is the direct cause of several optic neuropathies. Several studies have reported that the loss of p66Shc ameliorates neuronal injury and vascular abnormalities in ischemia-reperfusion (I/R) injury. However, whether p66Shc is involved in the loss of RGC remains unclear. Therefore, this study aimed to investigate the function of p66Shc due to retinal ischemia in mice. The retinal I/R model was constructed after an intravitreal injection of recombinant adeno-associated viruses (rAAV-EGFP or rAAV-p66Shc-EGFP) for 4 weeks. The expression of p66Shc was detected by western blotting, quantitative real-time polymerase chain reaction, and immunofluorescence staining. The survival of RGCs was determined using immunofluorescence staining. Retinal function was analyzed based on electroretinogram (ERG) findings. Retinal cell apoptosis was detected by TdT-mediated dUTP nick-end labeling staining. The protein expressions of Akt, phospho-Akt, Bax, and PARP were analyzed by western blotting. After rAAVs were successfully transfected, enhanced green fluorescent protein was expressed in all retinal cell layers, and the level of p66Shc after I/R injury was successfully reduced. We found that inhibition of p66Shc expression remarkably decreased the death of RGCs and prevented the loss of ERG a- and b-wave amplitudes caused by retinal ischemia. Mechanistically, downregulation of p66Shc resulted in reduced Bax, whereas increased phospho-Akt and PARP. Taken together, our study revealed that p66Shc acts through the Akt pathway to protect RGCs from retinal I/R injury-induced apoptosis and retinal dysfunction, making p66Shc a possible therapeutic target for glaucoma treatment.

7,8-Dihydroxyflavone alleviates apoptosis and inflammation induced by retinal ischemia-reperfusion injury via activating TrkB/Akt/NF-kB signaling pathway.

Retinal ischemia-reperfusion injury (RIRI) is of common occurrence in retinal and optic nerve diseases. The BDNF/TrkB signaling pathway has been examined to be neuroprotective in RIRI. In this study, we investigated the role of a potent selective TrkB agonist 7,8-dihydroxyfavone (DHF) in rat retinas with RIRI. Our results showed that RIRI inhibited the conversion of BDNF precursor (proBDNF) to mature BDNF (mBDNF) and increased the level of neuronal cell apoptosis. Compared with RIRI, DHF+RIRI reduced proBDNF level and at the same time increased mBDNF level. Moreover, DHF administration effectively activated TrkB signaling and and downstream Akt and Erk signaling pathways which increased nerve cell survival. The combined effects of mBDNF/proBDNF increase and TrkB signaling activation lead to reduction of apoptosis level and protection of retinas with RIRI. Moreover, it was also found that astrocytes labeled by GFAP were activated in RIRI and NF-kB mediated the increased expressions of inflammatory factors and these effects were partially reversed by DHF administration. Besides, we also used RNA sequencing to analyze the differently expressed genes (DEGs) and their enriched (Kyoto Encyclopedia of Genes and Genomes) KEGG pathways between Sham, RIRI, and DHF+RIRI. It was found that 1543 DEGs were differently expressed in RIRI and 619 DEGs were reversed in DHF+RIRI. The reversed DEGs were typically enriched in PI3K-Akt signaling pathway, Jak-STAT signaling pathway, NF-kB signaling pathway, and Apoptosis. To sum up, the DHF administration alleviated apoptosis and inflammation induced by RIRI via activating TrkB signaling pathway and may serve as a promising drug candidate for RIRI related ophthalmopathy.

Differential susceptibility of retinal ganglion cell subtypes against neurodegenerative diseases.

Retinal ganglion cells (RGCs) are essential to propagate external visual information from the retina to the brain. Death of RGCs is speculated to be closely correlated with blinding retinal diseases, such as glaucoma and traumatic optic neuropathy (TON). Emerging innovative technologies have helped refine and standardize the classification of RGCs; at present, they are classified into more than 40 subpopulations in mammals. These RGC subtypes are identified by a combination of anatomical morphologies, electrophysiological functions, and genetic profiles. Increasing evidence suggests that neurodegenerative diseases do not collectively affect the RGCs. In fact, which RGC subtype exhibits the strongest or weakest susceptibility is hotly debated. Although a consensus has not yet been reached, it is certain that assorted RGCs display differential susceptibility against irreversible degeneration. Interestingly, a single RGC subtype can exhibit various vulnerabilities to optic nerve damage in diverse injury models. Thus, elucidating how susceptible RGC subtypes are to various injuries can protect vulnerable RGCs from damage and improve the possibility of preventing and treating visual impairment caused by neurodegenerative diseases. In this review, we summarize in detail the progress and status quo of research on the type-specific susceptibility of RGCs and point out current limitations and the possible directions for future research in this field.

Identification of Survival-Related Metabolic Genes and a Novel Gene Signature Predicting the Overall Survival for Patients with Uveal Melanoma.

INTRODUCTION: Uveal melanoma (UM) is the most common primary intraocular malignancy among adults. Altered metabolism has been shown to contribute to the development of cancer closely, but the prognostic role of metabolism in UM remains to be explored. This study aimed to construct a metabolic-related signature for UM. METHOD: We collected the mRNA sequencing data and corresponding clinical information from The Cancer Genome Atlas and Gene Expression Omnibus databases. A univariate Cox regression analysis, the Lasso-penalized Cox regression analysis, and multivariate Cox regression analyses were used to construct a metabolic signature based on TCGA. The time-dependent ROC and Kaplan-Meier survival curves were calculated to validate the prognostic ability of the signature. The immune-related features and mutation profile were characterized by CIBERSORT and maftools between high- and low-risk groups. RESULT: A novel metabolic-related signature (risk score = -0.246*SLC25A38 - 0.50186*ABCA12 + 0.032*CA12 + 0.086*SYNJ2) was constructed to predict the prognosis of UM patients. In TCGA and GSE22138, the signature had high sensitivity and specificity in predicting the prognosis of UM patients (survival probability; p < 0.0001, p = 0.012) . Gene Ontology pathway enrichment analysis and GSEA were used to discriminate several significantly enriched metabolism-related pathways, including channel activity and passive transmembrane transporter activity, which may reveal the underlying mechanisms. The high-risk group had more immune cell infiltration and greater distribution of BAP1 mutations. CONCLUSION: Our study developed a robust metabolic-gene signature based on TCGA to predict the prognosis of UM patients. The signature indicates a dysregulated metabolic microenvironment and provides new metabolic biomarkers and therapeutic targets for UM patients.

Using methanol to preserve retinas for immunostaining.

BACKGROUND: Experimental studies on retinal vasculature and retinal ganglion cells (RGCs) investigating the developmental and pathological conditions of the retina mainly rely on whole-mount retinal immunostaining. Methanol, an auxiliary fixed medium for retinal whole-mount preparations, has been used in some studies; however, its application in short- and long-term storage of retinas for further study has not been well described. We aimed to evaluate methanol use as a preservation treatment for further immunostaining of the retina. METHODS: We generated oxygen-induced retinopathy (OIR) and optic nerve crush (ONC) mouse models and used their retinas for analysis. We pipetted cold methanol (-20°C) on the surface of the retina to help fix the tissues while promoting permeability, after which the retinas were stored in cold methanol (-20°C) for 1, 6, or 12 months before being evaluated using various optical techniques. Thereafter, retinal whole-mount immunostaining was performed to analyse retinal neovascularisation and retinal hypoxia in OIR model, and retinal ganglion cell survival rate in ONC model. RESULTS: Quantitative analysis revealed no significant differences in the fixed retinas after long-term storage in terms of retinal vasculature or retinal hypoxia in the OIR model. Similarly, no significant difference was found in RGC survival rate after long-term storage in methanol. These results suggest that methanol can be used as a storage medium when preserving retinal whole-mount samples. CONCLUSIONS: Cold (-20°C) methanol can serve as an effective medium for long-term storage of fixed retinas, which is useful for further research.

CM082, a novel VEGF receptor tyrosine kinase inhibitor, can inhibit angiogenesis in vitro and in vivo.

The goal of this study was to evaluate the effects of CM082, a novel vascular endothelial growth factor (VEGF) receptor-2 tyrosine kinase inhibitor, on human umbilical vein endothelial cells (HUVECs), and oxygen-induced retinopathy (OIR) mice. HUVECs were stimulated with rHuVEGF165 and then treated with CM082 to assess the antiangiogenic effects of CM082; subsequently, proliferation, wound-healing migration, Transwell invasion, tube formation assays, and Western blotting were performed in vitro. Retinal neovascularization tufts, avascular area, and TUNEL assays were estimated for OIR mice after intraperitoneal injection with CM082. CM082 significantly inhibited proliferation, migration, invasion, and tube formation induced by stimulation of HUVECs with rHuVEGF165; this inhibitory effect was mediated by blocking VEGFR2 activation. CM082 significantly inhibited retinal neovascularization and avascular area and did not increase apoptosis in the retina of OIR mice. The findings demonstrated that CM082 exhibits highly antiangiogenic effects in HUVECs and OIR mice. Thus, it may serve as an alternative treatment for neovascular eye disease in the future.

Resveratrol attenuates retinal ganglion cell loss in a mouse model of retinal ischemia reperfusion injury via multiple pathways.

BACKGROUND: Resveratrol (RES) is a natural polyphenol that has been shown to protect retinal ganglion cells (RGCs) following retinal ischemia reperfusion (I/R) injury. However, the molecular mechanisms of resveratrol function are yet to be fully elucidated. Thus, this study explored the potential mechanisms of resveratrol in vivo. METHODS: A retinal ischemia reperfusion injury model was established in adult male C57BL/6 J mice. Intraperitoneal injection of resveratrol was administered continuously for 5 days. RGC survival was determined by immunofluorescence staining with Brn3a. Flash electroretinography (ERG) was conducted to assess visual function. Proteins of HIF-1a, VEGF, p38, p53, PI3K, Akt, Bax, Bcl2, and Cleaved Caspase3 were detected using Western blot. RESULTS: RES administration significantly ameliorated retinal thickness damage and increased Brn3a stained RGCs 7 days after I/R injury. We also found that administration of RES remarkably inhibited the upregulation of mitochondrial apoptosis-related protein Bax and Cleaved Caspase3, as well as increased the expression of Bcl2. Furthermore, RES administration significantly suppressed the I/R injury-induced upregulation of the HIF-1a/VEGF and p38/p53 pathways, while activating the I/R injury-induced downregulation of the PI3K/Akt pathway. Moreover, RES administration remarkably improved retinal function after I/R injury-induced functional impairment. CONCLUSIONS: Our data demonstrated that resveratrol can mitigate retinal ischemic injury induced RGC loss and retinal function impairment by inhibiting the HIF-1a/VEGF and p38/p53 pathways while activating the PI3K/Akt pathway. Therefore, our results further reinforce that resveratrol has potential for treating glaucoma.

Krüppel-like factor 7 protects retinal ganglion cells and promotes functional preservation via activating the Akt pathway after retinal ischemia-reperfusion injury.

OBJECTIVE: The purpose of this study is to investigate the effects of Krüppel-like factor 7 (KLF7) on retinal ganglion cells (RGCs) and retinal function after retinal ischemia-reperfusion (RIR) injury in mice. METHODS: Male C57BL/6J mice were intravitreally injected with recombinant adeno-associated vectors (rAAV-KLF7-EGFP or rAAV-EGFP), and subsequently used to induce RIR injury. Retinal cryosections were used to access the efficacy of virus transfection, 1, 2, 3, and 4 weeks after rAAV-KLF7-EGFP transfer. RGCs survival rate was observed and quantified by immunofluorescent staining, 7 days after RIR injury. Meanwhile, electroretinogram (ERG) and optomotor response were used to evaluate the electrophysiological functions and visual acuity. Apoptosis was evaluated by TUNEL staining 1 day after RIR injury. Expression of KLF7, Akt, phospho-Akt, Bcl-2, and Bax were further detected by western blot to excavate the underlying mechanism. RESULTS: The transfection efficiency of rAAV-KLF7-EGFP was increased in a time-dependent manner, and the number of EGFP-positive cells was increased significantly 3 weeks after rAAV-KLF7-EGFP transfer. RGCs survival rates, amplitudes of ERG a-, b-wave, Ops, PhNR, and visual acuity of mice were decreased after RIR injury. With the increase of light intensity, the amplitudes of scotopic ERG a- and b-wave were gradually increased while the incubation period was gradually shortened. RGCs survival rates, amplitudes of ERG a-, b-wave, Ops, PhNR, and visual acuity of mice were increased after rAAV-KLF7-EGFP transfer. The protein level of KLF7 was up-regulated after rAAV-KLF7-EGFP transfer. Up-regulation of KLF7 significantly inhibited cells apoptosis, increased phospho-Akt and Bcl-2 expression, and decreased Bax expression. There were no significant changes in Akt expression. CONCLUSION: Overexpression of KLF7 can not only prevent the loss of RGCs, but also preserve the electrophysiological function. In addition, overexpression of KLF7 can ameliorate the retinal dysfunction after RIR injury, and ultimately improve the visual acuity of mice. The activation of Akt pathway and the suppression of the mitochondrial apoptotic pathway contribute to the neuroprotection of KLF7.

Application of platelet-rich fibrin grafts following pterygium excision.

PURPOSE: To compare the efficacy, safety and recurrence rate of platelet-rich fibrin (PRF) grafts and limbal conjunctival autografts (LCAs) following pterygium excision. METHODS: A total of 108 patients (108 eyes) with primary pterygium were included in this study and were divided into group A (56 eyes) and group B (52 eyes). Patients in group A underwent excision of the pterygium followed by LCA while patients in group B underwent PRF grafts following pterygium excision. The PRF was produced using the patient's own whole-blood sample by centrifugation and extrusion. The surgery time, intraoperative complications, postoperative complications, recurrence rate, intraocular pressure (IOP) and follow-up period were recorded and evaluated between the two groups. RESULTS: The mean surgery time was significantly shorter in group B (25.0 ± 4.2 min) than in group A (36.5 ± 6.3 min) (P < .001). Recurrence was observed in two cases (3.6%) in group A while no recurrence was observed in group B. No graft loss was observed in either group. No other intra/postoperative complications such as a tear in the graft, injury to the medial rectus muscle, excessive bleeding, scleral necrosis, graft oedema, graft necrosis, pannus formation or symblepharon appeared in either group. CONCLUSIONS: This study presented with a promising outcome of PRF graft applications in primary pterygium surgery. The use of PRF following pterygium excision is a simple, easily applicable, and comfortable method for both patients and surgeons, with less time consumption, recurrence rate and complications, which could be widely used in pterygium management.