Search Results (332)

Nicotinamide adenine dinucleotide (NAD⁺) boosting can sustain energy metabolism and neurovascular stability in the retinal tissue. Depletion of NAD⁺ is linked to the development of pathological retinal conditions, such as age-related macular degeneration (AMD) and diabetic retinopathy (DR). Mitochondrial dysfunction, oxidative stress, and inflammation occur in these diseases. This review summarizes substantial evidence of therapeutic NAD⁺ boosters, including nicotinamide, nicotinamide mononucleotide, or nicotinamide riboside. They help improve mitochondrial function and lessen neurovascular injury. We also emphasize the importance of natural products and sirtuins in facilitating cytoprotective effects through the regulation of mitochondrial balance and inflammation. Developments in drug delivery methods, such as nanoparticle encapsulation and targeted eye treatments, are promising for enhancing the bioavailability and effectiveness of NAD⁺ boosters. The novelty of this work is its combination of mechanistic insights regarding NAD⁺ metabolism with efficacy data from preclinical studies. Furthermore, natural products may work together to boost their therapeutic effects against retinal damage. Together, our review article highlights NAD⁺ metabolism as a potential therapeutic target for addressing retinal degeneration and maintaining vision in aging, neurologic disorders, and various metabolic diseases, including diabetes. Full article

Background: Blue light-induced retinal photodamage represents a growing public health concern globally. Lactic acid bacteria and their bioactive metabolites represent a promising therapeutic strategy for mitigating such damage. Methods: This study evaluated the protective efficacy of Limosilactobacillus fermentum IOB802 and Lactobacillus plantarum subsp. plantarum IOB602 against blue light-induced retinal injury using both in vitro and in vivo models. Results: In ARPE-19 cells exposed to blue light, treatment with postbiotics from IOB802 and IOB602 significantly restored cell viability (p < 0.05), enhanced antioxidant enzyme activities (GSH-Px, SOD, and CAT, p < 0.05), and reduced inflammatory cytokine levels (IL-6, IL-1β, TNF-α, and VEGF, p < 0.05). Subsequent validation in a murine blue light-induced retinal damage model demonstrated that IOB802 notably preserved retinal architecture, upregulated antioxidant defenses, and promoted the expression of tight junction proteins. Mechanistically, IOB802 suppressed inflammation by inhibiting the phosphorylation of the IκBα/NF-κB pathway. Through 16S rDNA sequencing and short-chain fatty acid (SCFA) profiling, IOB802 was further shown to restore gut microbial diversity, increase beneficial bacteria, including Lachnospiraceae, Rikenellaceae, and Bacteroidaceae (p < 0.05), and elevate concentrations of key SCFAs (butyrate, acetate, and propionate; p < 0.05), underscoring the role of the gut–retina axis in mediating retinal protection. Conclusions: In summary, IOB802 and its postbiotics alleviate blue light-induced retinopathy through antioxidative, anti-inflammatory, and microbiota-modulating mechanisms, offering novel insights into microbiome-based interventions for retinal diseases. Full article

Serotonin is a key neurotransmitter involved in visual processing. Selective serotonin reuptake inhibitors (SSRIs), such as Escitalopram, enhance serotonergic transmission and exert neuroprotective effects. Although these actions are well established in the central nervous system, their influence on retinal neurons remains unclear. This study investigated whether Escitalopram provides neuroprotection to retinal neurons following ischemic injury. Rats received Escitalopram or vehicle for 12 weeks. Retinal ischemia was induced by unilateral episcleral vein cauterization. A subset of animals received a retrobulbar injection of meclofenamic acid (MFA). Retinal function was assessed using electroretinography, intraocular pressure (IOP) was monitored, and retinas were collected for immunofluorescence and Western blot. Cauterization increased IOP in both groups, inducing retinal blood flow disturbances. Immunofluorescence showed a reduced number of retinal ganglion cells after cauterization, which was alleviated by SSRI treatment. Escitalopram also elevated expression of the brain-derived neurotrophic factor. Electroretinography revealed improved photopic negative response (PhNR) amplitudes in Escitalopram-treated rats, indicating improved retinal ganglion cell function. Following MFA, PhNR remained stable in SSRI-treated animals, whereas a significant impairment was observed in the vehicle-treated group. These findings demonstrate that Escitalopram provides neuroprotection by reducing both functional and structural damage in the retina and may represent a promising therapeutic strategy for retinal neurodegeneration. Full article

Neuroinflammation and oxidative stress are key drivers of various ocular diseases. Experimental hypoxia, modeled using cobalt chloride (CoCl₂), induces hypoxia-inducible factor 1-alpha (HIF-1α) stabilization, mitochondrial dysfunction, and excessive reactive oxygen species (ROS) production, primarily via the NADPH oxidase 2 (Nox2)–voltage-gated proton channel Hv1 axis. Although Botulinum neurotoxin type A (BoNT/A) is classically recognized for SNAP-25 cleavage, recent studies suggest broader anti-inflammatory and neuroprotective effects. We evaluated BoNT/A in R28 retinal precursor cells and ex vivo retinal explants subjected to CoCl₂-induced hypoxic stress. BoNT/A pretreatment attenuated CoCl₂-induced upregulation of HIF-1α, Hv1, Nox2, NOD-like receptor protein 3 (NLRP3), COX2, and nuclear factor kappa B (NF-κB), while enhancing protective mediators including suppressor of cytokine signaling 3 (SOCS3), Growth Associated Protein 43 (Gap43), and Syntaxin12. Brn3a expression and retinal architecture were preserved, apoptotic cell death reduced, and glial activation suppressed. Moreover, BoNT/A decreased mitochondrial ROS accumulation, restored voltage-dependent anion channel 1 (VDAC1) distribution, and partially stabilized intracellular pH. These findings indicate that BoNT/A mitigates oxidative stress and inflammation in hypoxia-driven retinal injury, at least in part, via modulation of the Nox2–Hv1–ROS axis, and support its potential as a therapeutic candidate for ocular disorders associated with hypoxia and neuroinflammation. Full article

Cell-based therapeutics are redefining interventions for vision loss by enabling tissue replacement, regeneration, and neuroprotection. This review surveys contemporary cellular strategies in ophthalmology through the lenses of therapeutic effectiveness, translational readiness, and governance. We profile principal sources—embryonic and induced pluripotent stem cells, mesenchymal stromal cells, retinal pigment epithelium, retinal progenitor and limbal stem cells—and enabling platforms including extracellular vesicles, encapsulated cell technology and biomaterial scaffolds. We synthesize clinical evidence across age-related macular degeneration, inherited retinal dystrophies, and corneal injury/limbal stem-cell deficiency, and highlight emerging applications for glaucoma and diabetic retinopathy. Delivery routes (subretinal, intravitreal, anterior segment) and graft formats (single cells, sheets/patches, organoids) are compared using standardized structural and functional endpoints. Persistent barriers include GMP-compliant derivation and release testing; differentiation fidelity, maturation, and potency; genomic stability and tumorigenicity risk; graft survival, synaptic integration, and immune rejection despite ocular immune privilege; the scarcity of validated biomarkers and harmonized outcome measures and ethical, regulatory, and health-economic constraints. Promising trajectories span off-the-shelf allogeneic products, patient-specific iPSC-derived grafts, organoid and 3D-bioprinted tissues, gene-plus-cell combinations, and cell-free extracellular-vesicle therapeutics. Overall, cell-based therapies remain investigational. With adequately powered trials, methodological harmonization, long-term surveillance, scalable xeno-free manufacturing, and equitable access frameworks, they may eventually become standards of care; at present, approvals are limited to specific products/indications and regions, and no cell therapy is the standard of care for retinal disease. Full article

Traumatic optic neuropathy (TON) causes vision loss through compression and contusion, yet there is no consensus on the most effective treatment. Polyunsaturated fatty acid (PUFA)-derived bioactive lipids metabolized by lipoxygenase (LOX), cytochrome P450 (CYP), and cyclooxygenase (COX) enzymes are known mediators of inflammation and neurodegeneration. However, their role in TON-related retinal pathology remains unclear. Controlled orbital impact (COI) was used to induce unilateral TON in mice with controlled velocity (2–3 m/s), with the fellow eye serving as an internal control. Retina tissues were collected three days post-injury and analyzed by LC/MS to quantify bioactive lipid metabolites from ω−6 and ω−3 PUFAs. Statistical analysis was performed using paired, nonparametric Wilcoxon signed-rank tests with Benjamini–Hochberg false discovery rate (FDR) correction. Results showed that among 38 reliably detected metabolites, no individual lipid showed a statistically significant difference between TON and control eyes after FDR correction (q < 0.05). However, both individual and pathway-level analysis revealed consistent trends toward increased expression of LOX- and CYP-derived metabolites across FDA PUFA substrates, including arachidonic acid (AA), linoleic acid (LA), and docosahexaenoic acid (DHA). These findings support further investigation into lipid-mediated inflammation in TON and its potential as a therapeutic target, particularly through expanding both the sample size and the post-TON time periods. Full article

Background/Objectives: Oxidative stress is the major cause of retinal pigment epithelial cell death. We used oxidative stress-injured retinal pigment epithelial cells to investigate the protective effects of curcumin, a strong antioxidant, on the Nod-like receptor protein 3 (NLRP3) inflammasome pathway. Methods: To evaluate the effect of curcumin, cell viability was measured with cell counting kit-8 and lactate dehydrogenase assays. Hydrogen peroxide (H₂O₂)-injured ARPE-19 cells were treated with different curcumin concentrations. We performed a wound healing assay and dichlorodihydrofluorescein diacetate staining. Western blotting and immunofluorescence staining were performed to evaluate the changes in inflammasome levels in the ARPE-19 cells. Result: H₂O₂ (300 μM) reduced the viability of ARPE-19 cells. However, treatment with 7.5 μM curcumin enhanced ARPE-19 cell viability and reduced cell toxicity. Curcumin also reduced reactive oxygen species (ROS) levels in the H₂O₂-induced damaged ARPE-19 cells and attenuated the H₂O₂-dependent levels of the NLRP3 inflammasome and its related signaling proteins. Conclusions: Curcumin demonstrated protective effects against oxidative stress in retinal pigment epithelial cells by attenuating the activation of the NLRP3 inflammasome pathway. These findings suggest the therapeutic potential of curcumin as an anti-inflammatory and antioxidant agent for macular degeneration. Full article

Background/Objectives: Retinal ischemia–reperfusion (I/R) injury is a common mechanism in glaucoma, diabetic retinopathy, and retinal vein occlusion, leading to progressive loss of retinal ganglion cells (RGCs). This study investigates the regulatory role of miR-21-5p and its interaction with Signal Transducer and Activator of Transcription 3 (STAT3) in retinal I/R injury. Methods: An acute intraocular hypertension (AIH) rat model was used to induce retinal I/R. The interaction between miR-21-5p and STAT3 was examined by dual-luciferase reporter assays. miR-21-5p and STAT3 expression were quantified by qRT-PCR and Western blotting. Retinal morphology, microglial polarization, and RGC survival were assessed by H&E staining and immunofluorescence. In vitro, microglia and RGCs were subjected to oxygen–glucose deprivation/reperfusion (OGD/R), and microglial-conditioned media (MCM) were applied to RGCs. Results: (1) miR-21-5p ameliorated AIH-induced retinal damage in vivo. (2) Overexpression of miR-21-5p inhibits M1 polarization of RM cultured in vitro. (3) MCM from miR-21-5p-overexpressing microglia attenuated OGD/R-induced RGC death. (4) miR-21-5p downregulates STAT3 expression to inhibit RM M1 polarization. (5) miR-21-5p down-regulation of STAT3 levels inhibits M1 polarization and reduces apoptosis of RGCs in retinal microglia of AIH rats. Conclusions: miR-21-5p alleviates retinal I/R injury by restraining microglial M1 polarization through direct repression of STAT3, thereby promoting RGC survival. These findings identify the miR-21-5p/STAT3 axis as a potential therapeutic target for ischemic retinal diseases. Full article

Diabetic retinopathy (DR) is a leading cause of vision loss globally and represents one of the most common microvascular complications of diabetes. In addition to metabolic disturbances associated with hyperglycemia, oxidative stress has emerged as a critical contributor to the onset and progression of DR. Oxidative stress, defined as an imbalance between the production of reactive oxygen species (ROS) and antioxidant defense mechanisms, leads to cellular injury, inflammation, and increased vascular permeability. In the diabetic retina, excessive ROS production promotes endothelial cell apoptosis, breakdown of the blood-retinal barrier (BRB), and induction of angiogenic factors such as vascular endothelial growth factor (VEGF). This review provides a comprehensive overview of the pathophysiology of DR, focusing on the molecular mechanisms of oxidative stress. Relevant studies were identified through a structured search of PubMed, Web of Science, and Scopus (2000–2025) using terms such as ‘diabetic retinopathy’, ‘oxidative stress’, and ‘antioxidants’. We explore current knowledge on oxidative stress-related biomarkers and therapeutic strategies targeting oxidative damage, including antioxidant compounds and mitochondrial protective agents. Recent findings from both experimental and clinical studies are summarized, highlighting the translational potential of oxidative stress modulation in DR management. Finally, future research directions are discussed, including biomarker standardization, personalized medicine approaches, and long-term clinical validation of antioxidant-based therapies. A deeper understanding of oxidative stress may offer valuable insights into novel diagnostic and therapeutic strategies for DR. Full article

In the last years, the zebrafish model has become a primary model system for vertebrate tissue regeneration, particularly for neurodegeneration and metabolic disease. Zebrafish (Danio rerio) are small freshwater teleosts valued for disease modelling, which are widely used in genetic laboratories, as a key model for studying neurodegenerative, metabolic, cardiac and dystrophic diseases, supporting the goal of identifying new therapeutic targets and approaches. Zebrafish can proliferate and produce/regenerate neurons. In response to retinal injury, zebrafish can regenerate multiple classes of retinal neurons and particularly, Müller glia-derived progenitor cells (MGPCs) can regenerate all types of neurons and restore visual function upon injury. The Jak/Stat-pathway of zebrafish retina represents one of the cell-signalling pathways involved in reprogramming Müller glia into MGPCs. In this era characterized by a revolution in experimental models and the future of omics, zebrafish might represent a suitable animal model for studying retinal degeneration and regeneration. In this context, the review is not meant to be entirely comprehensive of the zebrafish field, but it will highlight the usefulness of this model in discovering some mechanisms underlying retinal repair and regeneration. Full article

Low-density lipoprotein receptor-related protein 5 (LRP5) is a multifunctional transmembrane coreceptor that plays a pivotal role in development and disease. Wnt/β-catenin signaling is the primary downstream signaling pathway activated by LRP5. Furthermore, some LRP5 functions are mediated by noncanonical pathways, such as AKT/P21 and TGF-β/Smad signaling. Pathologically, both loss-of-function and gain-of-function mutations in LRP5 produce distinct phenotypes, ranging from osteoporosis-pseudoglioma syndrome to high bone mass disorders. Beyond the skeletal system, LRP5 has emerged as a key regulator of retinal angiogenesis, vascular integrity, renal tubular function, neurodevelopment, and lipid metabolism. Its physiological functions are highlighted by its ability to influence adipocyte differentiation, insulin sensitivity, and neuronal synaptic plasticity. Moreover, LRP5 displays a dual role in development and disease progression. Although it plays a protective role in acute injuries such as myocardial infarction and acute kidney injury, LRP5 also contributes to chronic pathologies such as tubulointerstitial fibrosis, polycystic kidney disease, and atherosclerosis through fibrotic and inflammatory pathways. Recent therapeutic interest has focused on modulating LRP5 activity using agents such as anti-Dickkopf-related protein 1 antibody, sclerostin inhibitors, polyclonal antibodies, CRISPR/Cas9 knockout, and some natural products. This review discusses the current understanding of LRP5's physiological and pathological roles across organ systems and highlights its therapeutic potential, emphasizing the need for targeted approaches considering its context-dependent effects. Full article

Dengue virus infection frequently involves the eye, manifesting with hemorrhages, uveal inflammation, retinal vascular changes and maculopathy. These ocular manifestations may arise during the acute febrile phase or emerge weeks later. Studies from endemic regions report that up to one-quarter of hospitalized patients develop eye-related symptoms. Furthermore, studies confirm a higher risk of new uveitis cases following dengue infection. Breakdown of the blood–ocular barrier—driven by antibody-mediated enhancement, complement activation and release of inflammatory mediators—leads to vascular leakage, tissue injury and ischemia. Diagnosis relies on clinical examination supplemented by imaging (OCT, angiography) and laboratory confirmation of dengue. Mild anterior inflammation often responds to topical steroids, while sight-threatening posterior disease requires systemic corticosteroids and, in refractory cases, immunomodulatory agents. Visual outcomes depend on the initial severity; anterior uveitis typically resolves without sequelae, whereas vasculitis or foveal involvement may leave lasting deficits. This review integrates the current understanding of dengue-related eye disease, emphasizing its varied presentations and the importance of early recognition. Further research into targeted, mechanism-based therapies is needed to optimize visual outcomes. Full article

Claudin 5 (Cldn5) is a critical tight junction protein essential for maintaining paracellular barrier integrity across endothelial and epithelial cells in barrier-forming tissues, including the blood–brain barrier and blood–retinal barrier. Cldn5 plays a central role in regulating vascular permeability, immune responses, and tissue homeostasis. The complex distribution and organ-specific regulation of Cldn5 underscore its potential as a promising therapeutic target. This review comprehensively analyzes the role of Cldn5 in endothelial and epithelial barrier function, its regulation of vascular permeability, and the discrepancies in the literature regarding its expression, regulation, and function in both physiological and pathological conditions across multiple organ systems, including the retina, brain, lung, heart, gut, kidney, liver, skin, and peripheral nerves, while emphasizing its tissue-specific expression patterns. We discuss how both reduced and excessive expressions of Cldn5 can disrupt barrier integrity and contribute to the pathogenesis of ischemic retinopathies, neuroinflammation, cardiovascular injury, and other forms of barrier dysfunction. Furthermore, we explore the dual role of Cldn5 as both a biomarker and a therapeutic target, highlighting emerging strategies such as RNA silencing, pharmacological stabilizers, and transcriptional modulators in controlling barrier leakage in disease conditions. Full article

Hydrogel-based vitreous substitutes have been considered as a potential solution for the treatment of retinal disorders, especially when the natural vitreous body is damaged due to trauma, disease, or surgery. With their high-water content, biocompatibility, and tunable mechanical properties, these hydrogels offer a promising alternative to traditional vitreous substitutes. This review explores the role of polymers and crosslinkers in the development of hydrogel-based substitutes, focusing on how these components contribute to the structure and function of hydrogels. The choice of natural polymers, such as hyaluronic acid and collagen, or synthetic ones, such as polyethylene glycol and polyvinyl alcohol, is crucial to mimic the transparency and flexibility of the vitreous body. Crosslinking methods, including physical, chemical, and enzymatic approaches, help control the gelation process and enhance the mechanical strength of the hydrogel. Furthermore, this review demonstrates how these hydrogels interact with biological tissues, which enhances biocompatibility, cell growth, and tissue repair. This review also discusses the challenges and future directions in improving these hydrogels, particularly in terms of long-term stability, integration with ocular tissues, and appropriate mechanical properties. Overall, hydrogel-based vitreous substitutes have significant potential to improve surgical outcomes and restore vision for patients with vitreous injury. Full article

Background/Objectives: Methamphetamine (METH), a potent psychostimulant, exerts harmful effects on the vascular system by promoting oxidative stress, inflammation, and endothelial injury. While its impact on the blood–brain barrier is well documented, its influence on the retinal microvasculature remains less understood. This study investigated the effects of METH on syndecan-1 expression and endothelial function in primary rat retinal microvascular endothelial cells (RRMECs) and isolated ophthalmic arteries. Methods: We assessed METH-induced changes in mRNA and protein expression levels of syndecan-1, matrix metalloproteinase (MMP)-2, and MMP-9. Endothelial function was evaluated using scratch migration assays and trans-endothelial electrical resistance (TEER) measurements. The mechanistic involvement of MMP-9 and trace amine-associated receptor 1 (TAAR-1), a known receptor for METH, was examined using selective pharmacological inhibitors. Results: METH exposure significantly decreased syndecan-1 expression and increased MMP-9 levels. These changes were accompanied by impaired endothelial migration and reduced TEER in RRMECs. Similar findings were confirmed in cultured ophthalmic arteries, reinforcing the translational relevance of our in vitro results. Inhibition of MMPs restored syndecan-1 expression and rescued endothelial function. Furthermore, TAAR-1 antagonism protected against syndecan-1 degradation, reduced MMP-9 upregulation, and improved endothelial migration and barrier resistance. Conclusions: Our findings suggest that METH induces loss of syndecan-1 and retinal vascular integrity by promoting TAAR-1–mediated MMP-9 upregulation. Targeting the TAAR-1/MMP-9 axis may offer a promising therapeutic strategy for preventing METH-induced microvascular damage in the retina. Full article