Apoptosis Of Ganglion Cells Research Articles

SMTP-44D alleviates diabetic retinopathy by suppressing inflammation and oxidative stress in in vivo and in vitro models.

Diabetic retinopathy (DR) is the leading cause of blindness among working-age adults, and inflammation and oxidative stress contribute to DR development. However, no effective treatments are currently approved for DR. Therefore, this study aimed to investigate the effects of SMTP-44D-a Stachybotrys microspora-derived compound with anti-inflammatory and antioxidant properties-on DR in in vivo and in vitro models. Diabetes was induced in rats using 60mg/kg streptozocin, followed by treatment with SMTP-44D every second day. Retinal function was assessed using electroretinography every 2 months for 8 months. SMTP-44D prevented diabetes-induced b-wave amplitude reductions in electroretinogram and decreased retinal ganglion cell apoptosis. SMTP-44D also reduced the accumulation of advanced glycation end-products (AGEs), AGE receptors, and 8-hydroxydeoxyguanosine in the retina. Furthermore, when rat retinal Müller cells were cultured in DMEM medium containing 35mM glucose (high glucose, HG) and treated with SMTP-44D for 24h, SMTP-44D mitigated cell death, reactive oxygen species production, and inflammatory cytokine levels in the cells. These findings suggest that SMTP-44D exhibits significant antioxidant and anti-inflammatory effects, highlighting its potential as a therapeutic candidate for DR.

SVM-Based Optical Detection of Retinal Ganglion Cell Apoptosis

Background: Retinal ganglion cell (RGC) loss is crucial in eye diseases like glaucoma. Axon damage and dendritic degeneration precede cell death, detectable within optical coherence tomography (OCT) resolution, indicating their correlation with neuronal degeneration. The purpose of this study is to evaluate the optical changes of early retinal degeneration. Methods: The detection of optical changes in the axotomised retinal explants was completed in six C57BL/6J mice. OCT images were acquired up to 120 min from enucleation. A grey-level co-occurrence-based texture analysis was performed on the inner plexiform layer (IPL) to monitor changes in the optical speckles using a principal component analysis (PCA) and a support vector machine (SVM). In parallel tests, retinal transparency was confirmed by a comparison of the modulation transfer functions (MTFs) at 0 and 120 min. Results: Quantitative confirmation by analysis of the MTFs confirmed the non-degradation of optical transparency during the imaging period: MTF (fx) = 0.267 ± 0.02. Textural features in the IPL could discriminate between the optical signals of RGC degeneration. The mean accuracy of the SVM classification was 86.3%; discrimination was not enhanced by the combination of the SVM and PCA (81.9%). Conclusions: Optical changes in the IPL can be detected using OCT following RGC axotomy. High-resolution OCT can provide an index of retinal neuronal integrity and its degeneration.

Dexamethasone-loaded fibroin nanoparticles promote retinal reattachment in rats by regulating the Th17/Treg balance

Retinal detachment (RD) is a common acute blinding eye disease, and dexamethasone (DEX), an adrenocorticosteroid, shows protective effects against RD. However, its poor water solubility and low bioavailability limit its effectiveness. To address this, we developed SF@DEX nanomaterials and investigated their therapeutic potential and mechanisms in RD. The nanomaterials were successfully synthesized and characterized, achieving 90% encapsulation efficiency and releasing 60% of DEX within 12 h.In vitro, phagocytosis was measured by flow cytometry, and enzyme-linked immunosorbent assay determined interleukin-17 (IL-17) and interleukin-10 (IL-10) levels. A rat RD model was established surgically, followed by oral administration of silk fibroin (SF), SF@DEX, and DEX. Polymerase chain reaction (PCR) assessed IL-17A and forkhead box P3 (FOXP3) expression, while Western blot analysed transforming growth factor-β1 (TGF-β1), IL-10, IL-17A, and FOXP3 levels. Apoptosis of retinal ganglion cells was evaluated using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and confocal microscopy detected colocalization of IL-17A and FOXP3. SF@DEX treatment significantly reduced Th17 cells and IL-17A while increasing Tregs, FOXP3, TGF-β1, and IL-10 levels. The severity of RD in rats was notably alleviated by SF@DEX, demonstrating its anti-inflammatory effects through modulation of the Th17/Treg immune balance. These results highlight SF@DEX as a promising nano-based therapy for RD.

Effect of Coenzyme Q10 in Inhibiting Retinal Ganglion Cell Apoptosis on Glaucomatous neuro degeneration Model

This study aimed to explore CoQ10 properties in inhibiting retinal ganglion cell (RGC) apoptosis in the glaucomatous animal model.A comprehensive literature search was performed in Medline/Pubmed, Science Direct, ProQuest, and Web of Science till August 8th, 2023. The authors conducted study selection, data extraction, and risk of bias assessment independently. This study was registered at PROSPERO (registration number CRD42023454777).A total of 5 studies which vary in glaucomatous animal models were selected. All the studies showed a decreased mean of apoptotic RGCs in the glaucomatous CoQ10-supplemented model compared to control. Studies suggest CoQ10 may modify Bax/Bad/BcL-xL-mediated apoptotic pathway.Oxidative stress was also shown to be decreased in several studies which was marked by reducing protective oxidative stress markers (SOD2; HO1).Further research on human subjects was needed to explore CoQ10 potentials.

Stem Cell-Based Therapies for Glaucoma Treatment: A Review Bridging the Gap in Veterinary Patients.

Retinal diseases are characterized by progressive damage to retinal cells, leading to irreversible vision loss. Among these, glaucoma stands out as a multifactorial neurodegenerative disease involving elevated intraocular pressure, retinal ganglion cell apoptosis, and optic nerve damage, ultimately resulting in blindness in both humans and dogs. Stem cell-based therapies have emerged as a promising therapeutic option for such conditions due to their regenerative and neuroprotective potential. These therapies, particularly those based on mesenchymal stem cells, offer the potential to repair and protect retinal tissues through the bioactive molecules (growth factors, cytokines, chemokines) secreted, their secretome. However, research in this field, especially on the use of umbilical cord mesenchymal stem cells' secretome, remains sparse. Most clinical trials focus on human glaucomatous patients, leaving a significant gap in veterinary patients' application, especially in dogs, with additional research being needed to determine its usefulness in canine glaucoma treatment. Future studies should aim to evaluate these therapies across both human and veterinary contexts, broadening treatment possibilities for glaucoma.

Unveiling Key Genes Modulating Retinal Cell Survival and Autophagy in Glaucoma.

Glaucoma is a leading cause of irreversible blindness, with rising incidence globally. Effective treatment is challenging due to limited understanding of the disease mechanisms. Growth factor activity is crucial in glaucoma, with potential to reduce retinal ganglion cell (RGC) apoptosis and slow disease progression. This study aims to identify and analyze differentially expressed genes (DEGs) involved in growth factor activity to uncover new therapeutic targets. We analyzed the GSE9944 dataset from the Gene Expression Omnibus (GEO) to identify DEGs associated with glaucoma, resulting in 94 DEGs, including 29 down-regulated and 65 up-regulated genes. Functional enrichment and protein-protein interaction (PPI) network analyses were conducted using bioinformatics tools, highlighting the roles of Bone Morphogenetic Protein 1 (BMP1), Pleiotrophin (PTN), and f fibroblast Growth Factor 7 (FGF7). Aberrant expression vectors for these genes were transfected into RGCs derived from a glaucoma model to evaluate their impact on cell viability, apoptosis, and autophagy. Bioinformatics analysis of the GSE9944 dataset identified 94 DEGs, with 29 down-regulated and 65 up-regulated genes. Functional enrichment analysis revealed that these DEGs were involved in pathways related to growth factor activity, apoptosis, and autophagy, processes highly relevant to glaucoma pathogenesis. PPI network analysis identified BMP1, PTN, and FGF7 as central hub genes involved in extracellular matrix organization and growth factor signaling. In experimental validation using RGCs, we found that up-regulation of BMP1 significantly enhanced RGC viability and reduced apoptosis. Conversely, silencing PTN and FGF7 provided protective effects, enhancing RGC survival. Silencing BMP1 and upregulating PTN and FGF7 led to increased RGC apoptosis. Additionally, BMP1 was found to inhibit autophagy in RGCs, whereas PTN and FGF7 promoted autophagic activity, suggesting differential regulatory roles in glaucoma pathogenesis. Overall, BMP1, PTN, and FGF7 play critical roles in the regulation of RGC activity and autophagy in glaucoma, making them promising molecular targets for future therapeutic interventions.

Preservation of Murine Whole Eyes With Supplemented UW Cold Storage Solution: Anatomical Considerations.

Retinal ganglion cell (RGC) apoptosis and axon regeneration are the principal obstacles challenging the development of successful whole eye transplantation (WET). The purpose of this study was to create a neuroprotective cocktail that targets early events in the RGC intrinsic apoptotic program to stabilize RGCs in a potential donor eye. University of Wisconsin (UW) solution was augmented with supplements known to protect RGCs. Supplements targeted tyrosine kinase signaling, histone deacetylase activity, K+ ion efflux, macroglial stasis, and provided energy support. Modified UW (mUW) solutions with individual supplements were injected into the vitreous of enucleated mouse eyes, which were then stored in cold UW solution for 24 hours. Histopathology, immunostaining of individual retinal cell types, and analysis of cell-specific messenger RNAs (mRNAs) were used to identify supplements that were combined to create optimal mUW solution. UW and mUW solutions reduced ocular edema and focal ischemia in globes stored in cold storage. Two major issues were noted after cold storage, including retinal detachment and reduction in glial fibrillary acidic protein staining in astrocytes. A combination of supplements resolved both these issues and performed better than the individual supplements alone. Cold storage resulted in a reduction in cell-specific mRNAs, even though it preserved the corresponding protein products. Eyes treated with optimal mUW solution exhibited preservation of retinal and cellular architecture, but did display a decrease in mRNA levels, suggesting that cold storage induced cellular stasis. Application of optimal mUW solution lowers an important barrier to the development of a successful whole eye transplantation procedure.

Autophagy-dependent ferroptosis may play a critical role in early stages of diabetic retinopathy.

Diabetic retinopathy (DR), as one of the most common and significant microvascular complications of diabetes mellitus (DM), continues to elude effective targeted treatment for vision loss despite ongoing enrichment of the understanding of its pathogenic mechanisms from perspectives such as inflammation and oxidative stress. Recent studies have indicated that characteristic neuroglial degeneration induced by DM occurs before the onset of apparent microvascular lesions. In order to comprehensively grasp the early-stage pathological changes of DR, the retinal neurovascular unit (NVU) will become a crucial focal point for future research into the occurrence and progression of DR. Based on existing evidence, ferroptosis, a form of cell death regulated by processes like ferritinophagy and chaperone-mediated autophagy, mediates apoptosis in retinal NVU components, including pericytes and ganglion cells. Autophagy-dependent ferroptosis-related factors, including BECN1 and FABP4, may serve as both biomarkers for DR occurrence and development and potentially crucial targets for future effective DR treatments. The aforementioned findings present novel perspectives for comprehending the mechanisms underlying the early-stage pathological alterations in DR and open up innovative avenues for investigating supplementary therapeutic strategies.

Overexpression of the inwardly rectifying potassium channel Kir4.1 or Kir4.1 Tyr9 Asp in Müller cells exerts neuroprotective effects in an experimental glaucoma model

Downregulation of the inwardly rectifying potassium channel Kir4.1 is a key step for inducing retinal Müller cell activation and interaction with other glial cells, which is involved in retinal ganglion cell apoptosis in glaucoma. Modulation of Kir4.1 expression in Müller cells may therefore be a potential strategy for attenuating retinal ganglion cell damage in glaucoma. In this study, we identified seven predicted phosphorylation sites in Kir4.1 and constructed lentiviral expression systems expressing Kir4.1 mutated at each site to prevent phosphorylation. Following this, we treated Müller glial cells in vitro and in vivo with the mGluR I agonist DHPG to induce Kir4.1 or Kir4.1 Tyr9Asp overexpression. We found that both Kir4.1 and Kir4.1 Tyr9Asp overexpression inhibited activation of Müller glial cells. Subsequently, we established a rat model of chronic ocular hypertension by injecting microbeads into the anterior chamber and overexpressed Kir4.1 or Kir4.1 Tyr9Asp in the eye, and observed similar results in Müller cells in vivo as those seen in vitro. Both Kir4.1 and Kir4.1 Tyr9Asp overexpression inhibited Müller cell activation, regulated the balance of Bax/Bcl-2, and reduced the mRNA and protein levels of pro-inflammatory factors, including interleukin-1β and tumor necrosis factor-α. Furthermore, we investigated the regulatory effects of Kir4.1 and Kir4.1 Tyr9Asp overexpression on the release of pro-inflammatory factors in a co-culture system of Müller glial cells and microglia. In this co-culture system, we observed elevated adenosine triphosphate concentrations in activated Müller cells, increased levels of translocator protein (a marker of microglial activation), and elevated interleukin-1β mRNA and protein levels in microglia induced by activated Müller cells. These changes could be reversed by Kir4.1 and Kir4.1 Tyr9Asp overexpression in Müller cells. Kir4.1 overexpression, but not Kir4.1 Tyr9Asp overexpression, reduced the number of proliferative and migratory microglia induced by activated Müller cells. Collectively, these results suggest that the tyrosine residue at position nine in Kir4.1 may serve as a functional modulation site in the retina in an experimental model of glaucoma. Kir4.1 and Kir4.1 Tyr9Asp overexpression attenuated Müller cell activation, reduced ATP/P2X receptor-mediated interactions between glial cells, inhibited microglial activation, and decreased the synthesis and release of pro-inflammatory factors, consequently ameliorating retinal ganglion cell apoptosis in glaucoma.

Genetic Insights and Epidemiological Models in Understanding Primary Open Angle Glaucoma

Primary open-angle glaucoma (POAG) is a multifactorial chronic optic neuropathy with significant genetic heterogeneity. The pathogenesis of POAG involves an imbalance between the production and drainage of aqueous humor (AH). Genetic theories suggest that transgenic mice demonstrating the GLU50LYS mutation in optineurin (OPTN) experience retinal ganglion cell apoptosis, while mutant myocilin (MYOC) proteins induce endoplasmic reticulum (ER) stress, leading to an unfolded protein response (UPR) and subsequent apoptosis of trabecular meshwork cells (TMC). Furthermore, the interaction between MYOC and mitochondria in the trabecular meshwork (TM) and astrocytes may lead to mitochondrial membrane depolarization and calcium channel dysregulation, contributing to POAG. Overexpression of MYOC variants (P370L, Q368X) is also implicated, as are epigenetic modifications and signaling pathways such as histone and DNA modification. POAG has been associated with autosomal dominant inheritance, with mutations in MYOC and OPTN being prominent causative factors, although many cases involve multiple genetic loci. Currently, over 20 genetic loci have been linked to POAG, with 14 chromosomal loci (GLC1A to GLC1N) identified, 5 of which contribute to juvenile-onset open-angle glaucoma (JOAG). Of these loci, MYOC, OPTN, WD repeat domain 36 (WDR36), and neurotrophin-4 (NTF4) are the most studied causative genes. The ongoing study of molecular genetics offers potential pathways for future therapeutic advances in the treatment of POAG.

GLCCI1 alleviates GRP78-initiated endoplasmic reticulum stress-induced apoptosis of retinal ganglion cells in diabetic retinopathy by upregulating and interacting with HSP90AB1

Retinal ganglion cells (RGCs) are among the first neurons to undergo apoptosis in diabetic retinopathy (DR), with their relationship to endoplasmic reticulum stress (ERS)-induced apoptosis still unclear. While glucocorticoid-induced transcript 1 (GLCCI1) has been shown to inhibit apoptosis, its role in ERS-induced apoptosis and its mechanisms in DR remain unclarified. Our findings indicated that GLCCI1 is predominantly localized in the ganglion cell layer and is downregulated in DR. GLCCI1 overexpression mitigated the apoptosis of RGCs and the swelling of endoplasmic reticulum and mitochondria under hyperglycemia, and downregulated ERS-induced apoptosis related markers (GRP78, CHOP and cleaved CASP3), whereas GLCCI1 knockdown has the opposite effect. In vivo, GLCCI1 overexpression not only prevents structural lesions but also protects against microvascular dysfunctions in the retinas of DR mice. We found that GLCCI1 directly interacts with HSP90AB1, which in turn interacts with GRP78. Additionally, GLCCI1 is an upstream regulator of HSP90AB1, which regulates GRP78. Thus, the impact of GLCCI1 on the ERS-induced apoptosis is mainly through the regulation of HSP90AB1, and subsequently inhibiting GRP78-initiated ERS-induced apoptosis. These findings offer a promising avenue for further treatment of DR.

Systematic Review and Meta-Analysis on the Association Between Daily Niacin Intake and Glaucoma.

Glaucoma is a progressive optic neuropathy, characterised by a complex pathophysiology, with mitochondrial dysfunction playing a significant role in the cellular damage and apoptosis of ganglion cells. Niacin is a precursor to several molecules acting as coenzymes in the mitochondrial production of ATP, in DNA repair and in the reduction of reactive oxygen species. The objective of this systematic review is to assess the impact of daily niacin intake on glaucoma. Case-control and cohort studies regarding niacin and glaucoma, indexed in PubMed, Web of Science, Cochrane and Scopus, were included. Other study methodologies, studies regarding niacin in other ocular disease or other nutrients in glaucoma were excluded. Bias was assessed using the Newcastle-Ottawa Scale. The study protocol was registered in the PROSPERO database (no. CRD42024578889). Five case-control studies were included. In the pooled analysis, a significantly higher proportion of patients with high niacin consumption was found in the group without glaucoma compared to those with glaucoma as defined by ISGEO criteria (p-value < 0.00001; OR = 0.66, 95% CI 0.55-0.79) or as defined by retinal imaging (p-value = 0.02; OR = 0.63, 95% CI 0.43-0.94). Daily dietary intake of niacin is significantly lower in patients with glaucoma compared to the general population. Given different average daily intakes of niacin in these populations, different glaucoma definitions and several confounding variables which weaken the associations, large sample, standardised randomised controlled trials are needed to confirm the potential benefits of niacin in glaucoma.

Research progress of retinal neuroprotective drugs for glaucoma

Glaucoma is a neural degenerative disease characterized by progressive loss of retinal ganglion cells, resulting in irreversible visual field loss, low vision, and total blindness. Despite the fact that the pathological elevation of intraocular pressure is a major risk factor for glaucoma, it is imperative to develop therapies that can prevent and block retinal ganglion cell injury and apoptosis in addition to reducing intraocular pressure. Drug therapy is the primary treatment for glaucoma in most clinical cases. This article provides reference information for the clinical treatment of glaucoma by summarizing and analyzing the medications that have direct optic nerve protection in clinical or preclinical trials, based on the most recent research results from both domestic and international studies.

Exploring the impact of oxidative stress, excitotoxicity, and apoptosis of retinal ganglion cells in streptozotocin-induced rats: A comprehensive investigation

Chronic hyperglycemia activates pathological molecular pathways, causing high inflammatory mediators, oxidative stress, and growth factors. This process contributes to retinal ganglion cell (RGC) apoptosis through the expression of N-methyl-D-aspartate (NMDA) receptors and nitric oxide (NO). This study analyzes the differential effect of NMDA receptor, NO expression, and RGC apoptosis in a hyperglycemic Wistar rat model. This research was designed as an experimental study, using a posttest only control group method. Fourteen male Wistar rats were split into two groups of seven: One received a single intraperitoneal injection of 50 mg/kg Streptozotocin (STZ) for hyperglycemia and the other served as the control. After 14 weeks of STZ injection, evaluations encompassed NMDA receptor, NO expression, and RGC apoptosis. Statistical analysis was performed using a parametric independent t-test and statistical significance was established at P &lt; 0.05. The hyperglycemic group showed much higher NMDA receptor levels (11.77 ± 3.36) than the control group (4.21 ± 2.16), with a P &lt; 0.001. The mean NO expression was 19.76 ± 8.41 in the hyperglycemic group, notably above the control group’s level of 4.01 ± 1.70 (P &lt; 0.001). The mean RGC apoptosis was 12.57 ± 3.26 in the hyperglycemic group and 9.00 ± 3.37 in the control group, without a significant difference, as indicated by a P = 0.068. These findings underscore the pronounced impact of hyperglycemia on NMDA receptors, NO expression, and RGC apoptosis, emphasizing potential targets for therapeutic interventions in diabetic retinopathy.

Erigeron breviscapus: A Promising Medication for Protecting the Optic Nerve in Glaucoma.

Glaucoma is a common eye condition characterized by the loss of retinal ganglion cells and their axons, optic nerve damage, and visual field defects, which seriously affect a patient's quality of life. The pathogenesis of glaucoma is still unclear at present. It presents as damage to retinal ganglion cells, and the main treatment is primarily to reduce intraocular pressure by surgery or taking medication. However, even with well-controlled intraocular pressure, retinal ganglion cells still undergo degeneration, progressive apoptosis, and axonal loss. Therefore, protecting the optic nerve and inhibiting the apoptosis of retinal ganglion cells are the current hot topic for prevention and treatment of glaucoma. Recently, Erigeron breviscapus, originating from Yunnan province in China, has been shown to be a promising herb with neuroprotective effects to treat glaucoma. Therefore, the traditional usage, botanical characteristics, and phytochemical composition of E. breviscapus were explored through a literature review. Furthermore, we have summarized the pharmacological mechanisms of E. breviscapus and its active components in inhibiting the apoptosis of retinal ganglion cells. These research findings can not only provide guidance and recommendations for the protection of retinal ganglion cells but also further explore the potential of E. breviscapus in the treatment of glaucoma.

Downregulation of LOX Overexpression Promotes Retinal Ganglion Cells Survival in an Acute Ocular Hypertension Model

Purpose To investigate the effect of reducing Lysyl oxidase (LOX) overexpression on retinal ganglion cells (RGCs) apoptosis in an acute ocular hypertension (AOH) rat model. Methods AOH rat model was performed by anterior chamber perfusion and either received an intravitreal injection with β-aminopropionitrile (BAPN) or normal saline. After 2wk, Quantification of survival RGCs in the retina was performed using Retrograde FluoroGold labeling. The mRNA expression levels of LOX, LOXL1-4, collagen 1a1 (Col1a1), collagen 3a1 (Col3a1), collagen4a1 (Col4a1), elastin (Eln), fibronectin1 (Fbn1), fibronectin4 (Fbn4) were determined by RT-qPCR. LOX expression was determined by Western blot (WB) analysis and immunohistochemistry. The RNA expression of LOX, Eln and Col1a1 in RGCs retrograde-labeled with 1,1’-dioctadecyl-3,3,3’,3’ tetra-methylindocarbocyanine perchlorate(DiI)that selected through FACS sorting were determined by RT-qPCR analysis. Changes of the retinal function were detected by Electroretinogram (ERG) analysis. Results Results showed that significant LOX overexpression and loss of RGCs related to IOP exposure in AOH retinas. PCR analysis indicated significant increased mRNA level of Col1a1, Col3al and Eln in AOH retinas. Significant increase mRNA expression of LOX, Col1a1 and Eln in the RGCs were observed in AOH group compared with CON group. AOH rats injected with BAPN showed a significant decrease in LOX expression, reduced the loss of RGCs and retinal function damage. Conclusions The results demonstrated that changes of LOX and specific ECM components in retina were correlated with AOH. Findings from this study indicated that preventing LOX over-expression may be protective against RGCs loss and retinal function damage in AOH animal model.

Is microbiota a factor in the mechanism of glaucoma development?

Nowadays, glaucoma is viewed as a multifactorial neurodegenerative condition that involves many factors affecting different cell types in a human body. As is known, increased intraocular pressure (IOP) is not the only threatening factor of ganglion cell apoptosis and glaucomatous optic neuropathy development; IOP can be associated with other factors, such as vascular, metabolic, neurotrophic, immune, inflammatory, etc. However, the treatment of glaucoma remains largely symptomatic, aimed almost exclusively at reducing IOP. Microbiotic dysbiosis is a newly developing research direction of the glaucomatous progress, showing that this mechanism may turn out to be an important factor of glaucoma development. There are reasons to believe that treatment strategies aimed at microbiota damage correction may contribute to a better efficiency of glaucoma management.

Histone Deacetylases in Retinoblastoma.

Retinoblastoma, a pediatric ocular malignancy, presents significant challenges in comprehending its molecular underpinnings and targeted therapeutic approaches. The dysregulated activity of histone deacetylases (HDACs) has been associated with retinoblastoma pathogenesis, influencing critical cellular processes like cell cycle regulation or retinal ganglion cell apoptosis. Through their deacetylase activity, HDACs exert control over key tumor suppressors and oncogenes, influencing the delicate equilibrium between proliferation and cell death. Furthermore, the interplay between HDACs and the retinoblastoma protein pathway, a pivotal aspect of retinoblastoma etiology, reveals a complex network of interactions influencing the tumor microenvironment. The examination of HDAC inhibitors, encompassing both established and novel compounds, offers insights into potential approaches to restore acetylation balance and impede retinoblastoma progression. Moreover, the identification of specific HDAC isoforms exhibiting varying expression in retinoblastoma provides avenues for personalized therapeutic strategies, allowing for interventions tailored to individual patient profiles. This review focuses on the intricate interrelationship between HDACs and retinoblastoma, shedding light on epigenetic mechanisms that control tumor development and progression. The exploration of HDAC-targeted therapies underscores the potential for innovative treatment modalities in the pursuit of more efficacious and personalized management strategies for this disease.

SiRNA Mediated Downregulation of RhoA Expression Reduces Oxidative Induced Apoptosis in Retinal Ganglion Cells.

Glaucoma is the second leading cause of blindness. Apoptosis of retinal ganglion cells (RGCs) is an important mechanism of glaucomatous optic injury. Rho kinase expression is significantly increased in apoptotic RGCs. This study aimed to investigate the role of RhoA, a Rho GTPase, on the survival of RGCs and further to explore its potential therapeutic applications. RGCs were treated with siRhoA for 24 hours in vitro. Knockdown of RhoA was confirmed with quantitative RT-PCR. Oxidative stress was induced by treating the RGCs with 200 μM of H2O2 for 1 hour, and apoptosis of RGCs was quantified with TUNEL assay in situ, and with flow cytometry. The mRNA expression levels of RhoA, Nogo receptor, caspase 3 and Bcl-2 were evaluated by quantitative RT-PCR, and the protein levels of RhoA, ROCK1, ROCK2, Nogo receptor, caspase 3 and Bcl-2 were evaluated by Western blot. We found siRhoA treatment efficiently downregulated the expression of RhoA in RGCs and protected against H2O2-induced injury in RGCs in vitro. Apoptosis of RGC cells under oxidative stress was quantified in situ using TUNEL assay and confirmed with flow cytometry (FCM). With the knockdown of RhoA, the expression of ROCK1, ROCK2, Nogo Receptor, Casepase-3 were decreased, while the expression of Bcl-2 was increased in both mRNA and protein level. Our data indicated that siRhoA prevented H2O2-induced apoptosis in RGC cells by modulating the RhoA/ROCK pathway. The results suggested that siRhoA may exert potentially effective neuroprotection for RGCs by reducing injury.

Resveratrol protects against diabetic retinal ganglion cell damage by activating the Nrf2 signaling pathway

ObjectiveOxidative stress-induced retinal neurodegenerative changes are among the pathological alterations observed in diabetic retinopathy. Resveratrol (RSV), a polyphenolic compound with diverse pharmacological effects, has shown preventive qualities in several neurodegenerative illnesses, including anti-inflammatory, anti-aging, and antioxidant benefits. However, its therapeutic efficacy in diabetic retinal neurodegeneration has not yet been thoroughly elucidated. Our study aimed to explore the protective mechanisms and therapeutic benefits of RSV on diabetic retinal neurodegeneration alterations. Materials and methodsUsing streptozotocin, we created a diabetic mouse model and conducted visual electrophysiological examinations on mice from the normal group, diabetic group, and diabetic group treated with RSV. Retinas were harvested for histological staining. Additionally, primary retinal ganglion cells cultured in high glucose conditions were used to assess malondialdehyde (MDA) levels and superoxide dismutase (SOD) levels upon siRNA-mediated nuclear factor erythroid 2-related factor 2 (Nrf2) interference. Protein levels of Nrf-2, heme oxygenase-1 (HO-1), and transcriptional levels of them were also measured. ResultsWe demonstrated that RSV significantly improved the retinal morphology and function in the diabetic retinopathy model mice. The treated mice exhibited notable improvements in visual electrophysiology, with a significant reduction in retinal ganglion cell apoptosis. Following RSV treatment, the high glucose-cultured ganglion cells demonstrated a considerable rise in SOD levels and a substantial drop in MOD. Moreover, the protein expression of solute carrier family 7 member 11 (SLC7A11) and Nrf2 significantly increased. RT-PCR and Western blot results indicated a significant attenuation of RSV's therapeutic effects upon Nrf2 inhibition. ConclusionOur findings suggest that RSV may reduce oxidative stress levels in the retina and inhibit retinal ganglion cell apoptosis via reducing the Nrf2/HO-1 pathway, which lessens the harm that excessive glucose causes to the retina.