Search Results (153)

Oxidative stress contributes to retinal neurovascular injury through inflammation, mitochondrial dysfunction, blood–retinal barrier (BRB) disruption, microcirculatory impairment, and regulated cell death. Hydroxysafflor yellow A (HSYA), a water-soluble quinochalcone C-glycoside derived from safflower (Carthamus tinctorius L.), modulates oxidative and inflammatory signaling, apoptosis, mitochondrial injury, endothelial barrier dysfunction, and neurovascular damage in experimental ischemic, inflammatory, and metabolic disorders. This review critically evaluates the direct ocular evidence for HSYA in diabetic retinopathy and examines the systemic-to-ocular pharmacokinetic and delivery barriers that constrain its ophthalmic translation. Current ocular evidence is limited and concentrated mainly in DR models, in which HSYA attenuates oxidative stress, inflammation, BRB disruption, and apoptosis, potentially through Nrf2/HO-1 signaling. Evidence in retinal photic injury is limited, whereas the proposed relevance of HSYA to retinal ischemia–reperfusion injury, glaucoma, and AMD remains largely hypothesis-generating. The principal translational challenge is whether HSYA can achieve pharmacologically relevant exposure in ocular target tissues. Future studies should integrate dose, plasma and ocular exposure, target engagement, retinal structure, local safety, and visual function in disease-specific models. Accordingly, evidence from non-DR models is discussed primarily to define mechanistic hypotheses and experimental priorities rather than to establish ophthalmic efficacy. Full article

Non-invasive drug delivery for ocular diseases remains a significant challenge in ophthalmology, as conventional eye drops offer less than 5% bioavailability due to pre-corneal barriers and the corneal epithelium. This review explores the intranasal (IN) route as a promising strategy for targeting both the anterior and posterior segments of the eye. The IN route leverages several distinct pathways: the nasolacrimal reflex for remote physiological stimulation; the “neural bridge” through the cribriform plate, allowing direct perineural and vascular transport via the olfactory and trigeminal nerves to bypass the blood–retinal barrier; and systemic absorption that avoids hepatic first-pass metabolism. Pre-clinical evidence indicates that IN administration of agents such as erythropoietin, nerve growth factor, and insulin achieves superior retinal concentrations compared to topical or systemic dosing, offering neuroprotection in models of retinal degeneration and glaucoma. Clinically, varenicline nasal spray is already FDA-approved for dry eye disease, while intranasal steroids demonstrate a favorable ocular safety profile without significantly increasing intraocular pressure. Although limited by mucociliary clearance and small delivery volumes, the IN route offers a painless, non-invasive alternative to intraocular injections, potentially enhancing patient compliance. Future advancements in mucoadhesive nanocarriers are essential to optimize drug residence time and realize the full potential of nose-to-eye delivery in chronic ophthalmic care. Full article

Glaucoma is a collection of disorders that result in permanent vision loss and is characterized by a gradual decline in retinal ganglion cells. While it may not always be high, intraocular pressure (IOP) is the sole risk factor that can be modified according to extensive clinical research. Glaucoma remains the leading cause of irreversible blindness, yet early treatment lowering intraocular pressure is effective in slowing the rate of visual deterioration. Issues like poor absorption, low bioavailability, and short drug resistance time have thus made the management of glaucoma challenging when using conventional ophthalmic drugs. Thus, extensive research has been conducted to explore specific nanodrug delivery systems from various nanocarriers such as nanoparticles, micelles, liposomes and nanofibers, with a focus on systems that have achieved drug release for more than 12 h. These carriers have demonstrated substantial improvements in a lot of the evaluated aspects: enhancing ocular barrier-crossing capabilities, improving bioavailability, prolonging drug release, targeting active tissues of interest, and reducing IOP. This review covers recent developments in nanocarrier ocular delivery systems regarding the management of glaucoma. In this study, the advantages and disadvantages of each system were evaluated and their potential for advancing translation from research to clinic were assessed. Full article

Background: Posterior segment eye diseases, including age-related macular degeneration and diabetic retinopathy, are preeminent causes of vision loss worldwide. Effective drug delivery to the retina poses an ongoing therapeutic difficulty due to the presence of the anatomical and physiological barriers. Nanotechnology-based drug delivery systems represent a promising strategy to overcome those limitations. Methods: A narrative literature review was conducted using the PubMed, Scopus, and Google Scholar databases, covering publications published between 2019 and 2026. Publications evaluating nanoparticles for the treatment of the vitreoretinal disorders, including pre-clinical in vitro and in vivo studies, were analyzed. Results: Nanocarriers, including liposomes, polymeric nanoparticles, and lipid-based systems, established improved drug bioavailability, stability, and targeted delivery. The analyzed systems facilitate sustained drug release and potentially reduce the prevalence of invasive intravitreal injections. The nanocarriers’ effectiveness is primarily influenced by their physicochemical properties, such as particle size, surface charge, and encapsulation efficiency. Nonetheless, the production costs and safety aspects, including cytotoxicity, oxidative stress, and inflammatory responses, remain as significant limitations. Conclusions: Nanotechnology-based drug delivery systems serve as an auspicious therapeutic approach for posterior segment eye diseases. However, further standardized preclinical and clinical research is required to assure long-term safety and enable successful clinical transition. Full article

In carbon monoxide (CO) therapy, CO is administered at low concentrations as a controlled solution; this approach enables the drug to achieve its cytoprotective properties, including anti-inflammatory, anti-apoptotic, and vasodilatory effects. CO therapy, initially reported to benefit cardiovascular and pulmonary conditions, is now used to treat ocular diseases in preclinical models. Carbon monoxide, a compound most famously known for its deleterious effects, is receiving more attention as a potential therapeutic candidate in ocular medicine. In a few studies, controlled low-dose CO therapy has shown anti-inflammatory and anti-apoptotic effects in various models of retinal disease (such as retinal ischemia-reperfusion injury, optic nerve crush, ocular hypertension, and autoimmune uveitis). We have summarized the clinical and preclinical findings, along with the potential therapeutic value of CO, in this review. In this context, the current and emerging CO delivery methods are also described, with a focus on exploring their safety, efficacy, and applicability in retinal disorders. Although a strong preclinical paradigm exists, clinical translation is limited at best. While some trials indicate acceptable safety levels for inhaled CO or CORM-based interventions, these results have not been robust or reproducible. Bridging this efficacy gap will rely on enhanced delivery strategies, stringent PK/PD-informed dosing, and mechanism-specific endpoint-based trials. Full article

Ocular disorders such as keratitis, glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR), and dry eye disease (DED) are highly prevalent worldwide and remain major causes of visual impairment and blindness. Conventional therapeutic approaches for ocular diseases, such as eye drops, surgery, and laser therapy, are frequently hampered by limited drug bioavailability, rapid clearance, and treatment-related complications, primarily due to the eye’s unique anatomical and physiological barriers. Hydrogels, characterized by their three-dimensional network structure, high water content, excellent biocompatibility, and tunable physicochemical properties, have emerged as promising platforms for ophthalmic drug delivery. This review summarizes the classification, fabrication strategies, and essential properties of hydrogels, and highlights recent advances in their application to ocular diseases, including keratitis management, corneal wound repair, intraocular pressure regulation and neuroprotection in glaucoma, sustained drug delivery for AMD and DR, vitreous substitutes for retinal detachment, and therapies for DED. In particular, we highlight recent advances in stimuli-responsive hydrogels that enable spatiotemporally controlled drug release in response to ocular cues such as temperature, pH, redox state, and enzyme activity, thereby enhancing therapeutic precision and efficacy. Furthermore, this review critically evaluates translational aspects, including long-term ocular safety, clinical feasibility, manufacturing scalability, and regulatory challenges, which are often underrepresented in existing reviews. By integrating material science, ocular pathology, and translational considerations, this review aims to provide a comprehensive framework for the rational design of next-generation hydrogel systems and to facilitate their clinical translation in ophthalmic therapy. Full article

Objective: Glaucoma is a complex optic neuropathy characterized by the progressive loss of retinal ganglion cells (RGCs). Animal models are crucial tools for deciphering its multidimensional pathogenesis and evaluating novel therapeutic strategies. This review aims to systematically summarize the establishment methods, application advances, and future development trends of various glanimal models. Methods: The literature for this review was identified through systematic searches of electronic databases, including PubMed, Web of Science Core Collection, and Google Scholar. The search strategy utilized a combination of keywords and their variants: “glaucoma”, “animal models”, “retinal ganglion cells”, “intraocular pressure”, “neuroprotection”, “immune inflammation”, “fibrosis”, and “filtration surgery”. The search focused on articles published between 2015 and 2025 to cover the major advances of the last decade. The scope encompassed original research articles, reviews, and meta-analyses. Results: Diverse glanimal models successfully replicate different facets of glaucoma, elucidating multidimensional pathogenesis involving mechanical stress, immune inflammation, excitotoxicity, oxidative stress, and fibrosis. These models have played an indispensable role in screening neuroprotective agents, evaluating anti-fibrotic strategies, and validating the application of advanced imaging and functional assessment technologies. Current research is evolving towards model standardization, multi-factor simulation, and the integration of novel drug delivery systems and immunomodulatory strategies. Conclusions: The diversification of glanimal models provides a powerful platform for in-depth investigation of disease mechanisms and the development of innovative therapies. Future research should focus on establishing standardized models that better mimic the clinical pathological state and deeply integrating multimodal assessment technologies with targeted therapies. This will facilitate the translation of basic research into clinical applications, ultimately achieving personalized precision medicine for glaucoma. Full article

Background/Objectives: Antimicrobial resistance (AMR) in ocular infections has become a serious concern with major implications for vision preservation. Bacterial AMR contributed to 4.71 million deaths worldwide in 2021, and ophthalmology mirrors these trends with multidrug resistance rates as high as 66% documented in some regions and persistently high methicillin resistance among common ocular pathogens. Across regions and care settings, traditional empiric therapies are losing effectiveness against an expanding range of pathogens, resulting in slower recovery, more complications, and, in many cases, permanent vision loss. This review aims to synthesize recent clinical, microbiologic, and pharmacologic evidence on ocular AMR, focusing on recent studies to capture current resistance patterns, therapeutic challenges, and evolving management strategies. Methods: Most included papers were published between 2020 and 2025, with additional foundational studies referenced where appropriate. Reports and systematic reviews addressing bacterial, viral, fungal, and parasitic ocular pathogens were evaluated to characterize current resistance mechanisms and management strategies across ocular pathogens. Results: The eye’s anatomic and physiologic barriers limit drug penetration, often promoting resistance and reducing therapeutic efficacy. Resistance mechanisms vary by pathogens; Pseudomonas keratitis is driven mainly by efflux pumps and biofilm formation, while CMV retinitis’ mutations in UL97 and UL54 are linked with clinical failure, and in MRSA associated Staphylococcus keratitis, the presence of mecA necessitates vancomycin-based therapy across bacterial, viral, fungal, and parasitic infections, with mechanisms such as β-lactamase production, efflux pump overexpression, target-site mutation, and biofilm formation contributing to poor response to standard therapy. MDR Pseudomonas keratitis remains the leading cause of rapidly progressive corneal infection with high risk of perforation and vision loss, while resistant CMV retinitis continues to threaten sight in immunocompromised patients despite antiviral advances. MDR organisms are recalcitrant to treatment and may lead to longer treatment courses and potentially worse outcomes and are discussed in detail within the manuscript. Conclusions: Ocular AMR represents an urgent and expanding clinical challenge. This review centers on the two most encountered multidrug-resistant organisms and their corresponding ocular sites, Pseudomonas aeruginosa (anterior segment) and CMV (posterior segment), while contextualizing them within the broader spectrum of resistant bacterial, viral, fungal, and parasitic pathogens. Despite growing awareness of AMR in ophthalmology, comprehensive surveillance data and longitudinal epidemiologic studies remain limited, making it difficult to track evolving resistance trends or guide region-specific therapy. Preserving vision in the AMR era will require faster diagnostics, improved ocular drug-delivery systems, and pathogen-specific therapies. Full article

Background and Objectives: Age-related macular degeneration (AMD) is an age-associated retinal disorder characterized by blood–retinal barrier (BRB) breakdown and pathological angiogenesis, leading to vascular leakage. The intravitreal administration of anti-VEGF agents remains the most effective treatment for neovascular AMD. However, repetitive intravitreal injections have risks, causing side effects such as cataracts, bleeding, retina damage, and, in severe cases, post-injection endophthalmitis. Hence, the development of innovative drug delivery systems is essential to minimize the risks and discomfort associated with intravitreal injections. Materials and Methods: We developed a microemulsion (ME)-based topical drug delivery system incorporating α-linolenic acid (ALA). In brief, pseudo-ternary phase diagrams were constructed by the water titration method using different combinations of surfactants and cosurfactants (S_mix-Cremophor RH 40: Span 80: Transcutol P in ratios of 1:1.05, 1:1:1, 1:1:1.5) containing ALA as the oil phase. Three blank microemulsions (ME1, ME2, and ME3) were prepared and characterized based on the optimized pseudo-ternary phase equilibrium with a S_mix ratio of 1:1:1. Results: ME3, with an average particle size of 38.59 nm, was selected as the optimized formulation for developing drug-loaded ME containing Fenofibrate, Axitinib, and Sirolimus. The drug-loaded ME showed particle size (46.94–56.39 nm) and in vitro release displayed sustained and longer time drug release for 240 h. The irritation and antiangiogenic activities were evaluated using the hen’s egg chorioallantoic membrane (HET-CAM) assay employing the optimized ME loaded with each drug. Among the three drug-loaded ME, the Sirolimus ME showed a reduction in blood vessel sprouting in the HET-CAM assay, indicating strong antiangiogenic activity. Treatment with the optimized blank ME and Sirolimus ME significantly (p < 0.05) reduced COX-2 protein expression in LPS-stimulated RAW 264.7 cells, suggesting their potential anti-inflammatory effects. Conclusions: Overall, we suggest that the α-linolenic acid-based Sirolimus microemulsion may serve as a promising topical therapeutic approach for managing AMD and offering a potential alternative to invasive intravitreal injections. Full article

The retinal pigment epithelium (RPE) is essential for maintaining retinal integrity, and its dysfunction underlies several progressive ocular diseases, including age-related macular degeneration, choroidal neovascularization (CNV), inherited retinal disorders (IRDs), and proliferative vitreoretinopathy (PVR). Although current therapies have improved disease management, they mainly target secondary pathological mechanisms and do not directly preserve or restore RPE function. Moreover, the delivery of therapeutic molecules or genes to the RPE remains a major challenge due to the presence of multiple ocular barriers and the need for sustained, localized action. Nanomedicine offers innovative solutions to these limitations by enabling precise, controlled, and cell-specific delivery of drugs and genetic materials. Engineered nanocarriers can be optimized to traverse ocular barriers, enhance bioavailability, and modulate the retinal microenvironment. This review summarizes recent advances in nanoscale delivery systems for RPE-targeted therapies, focusing on design principles, targeting strategies, and therapeutic applications, and discusses the translational challenges that must be addressed to bring nanotechnology-based treatments closer to clinical application. Full article

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/Objectives: Glaucoma is a neurodegenerative optic disorder which occurs due to persistent elevation of the intraocular pressure. It leads to permanent blindness and currently affects over 75 million individuals worldwide. Nowadays, topical ocular medications are the leading therapy despite their poor ocular penetration and short residence time. Methods: The purpose of this research is to formulate bisoprolol hemifumarate-loaded polylactic-co-glycolic acid (PLGA) nanoparticles and improve their ocular penetration and bioavailability for the treatment of glaucoma by enhancing the delivery of the drug to the posterior part of eye. By using the solvent displacement method, formulations were prepared and optimum formula was elected using Design-Expert^® software. Results: In vitro characterization demonstrated that the optimum formula contained 25 mg BSP, 22.5 mg PLGA, and 60 mg Tween80, yielding high values of drug encapsulation (75%) and zeta potential (−18.7 ± 0.41 mV), with a low particle size (105 ± 0.35 nm) and polydispersity index (0.411 ± 0.71). Transmission electron microscopy and atomic force microscopy showed smooth and spherical nanosized particles. X-ray diffraction, differential scanning calorimetry, and Fourier-transform infrared spectroscopy revealed successful encapsulation of the drug inside the polymeric matrix. Ex vivo confocal laser scanning microscopy proved that there was better uptake of the drug upon using PLGA-NPs. In vitro release profiles indicated biphasic drug release from the PLGA-NPs, confirming a sustained drug release over 12 h. In vivo studies showed that BSP-PLGA-NPs significantly reduced the IOP compared to bisoprolol solution. Quantitative immunohistochemistry showed lower retinal GFAP expression with BSP-PLGA-NPs compared with induced controls and drug solution, which is indicative of attenuated glial activation. Conclusions: These data support improved ocular delivery and an improved pharmacodynamic effect; however, they demonstrate association rather than a direct mechanistic suppression of glial pathways. Full article

Age-related macular degeneration (AMD) is a leading cause of irreversible visual impairment in the elderly, and oxidative stress, primarily mediated by reactive oxygen species (ROS), is widely recognized as a central driver of its onset and progression. The retina is highly susceptible to oxidative damage due to its elevated oxygen consumption, abundant polyunsaturated fatty acids, and continuous exposure to light. Recent studies have elucidated molecular mechanisms in which mitochondrial dysfunction, disruption of redox homeostasis, inflammation, and complement activation interact to promote degeneration of retinal pigment epithelium (RPE) and photoreceptor cells. In addition to age-related oxidative stress, environmental factors such as motor vehicle exhaust and volatile organic compounds (VOCs) can accelerate the accumulation of lipofuscin and drusen, thereby fostering a chronic pro-inflammatory milieu. From a therapeutic perspective, beyond conventional antioxidant supplementation, emerging strategies targeting oxidative stress-related pathways have gained attention, including mitochondrial protectants, activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, anti-inflammatory agents, and gene therapy. Importantly, several innovative approaches are under investigation, such as saffron supplementation with neuroprotective properties, drug repositioning of levodopa, and nanotechnology-based delivery systems to enhance retinal bioavailability of antioxidants and gene therapies. This review summarizes the pathophysiological role of oxidative stress in AMD from a molecular mechanistic perspective and discusses recent advances in research and novel therapeutic targets. Full article

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide exerting, among others, strong trophic and protective effects. It plays a role in several physiological functions, including glucose homeostasis. The protective effects of PACAP are mainly mediated via its specific PAC1 receptor by stimulating anti-inflammatory, anti-apoptotic and antioxidant pathways. The aim of the present review is to summarize data on the protective effects of PACAP in the three major complications of diabetes, retinopathy, nephropathy and neuropathy, as well as some other complications. In type 1 and type 2 diabetic retinopathy models and in glucose-exposed cells of the eye, PACAP counteracted the degeneration of retinal layers and inhibited apoptosis and factors leading to abnormal vessel growth. In models of nephropathy, kidney morphology was better retained after PACAP administration, with decreased apoptosis and fibrosis. In diabetic neuropathy, PACAP protected against axonal–myelin lesions and less activation in pain processing centers. This neuropeptide has several other beneficial effects in diabetes-induced complications like altered vascular response, cognitive deficits and atherosclerosis. The promising therapeutic effects of PACAP in several pathological conditions have encouraged researchers to design PACAP-related drugs and to develop ways to enhance tissue delivery. These intentions are expected to result in overcoming the hurdles preventing PACAP from being introduced into therapeutic treatments, including diabetes-related conditions. Full article

Age-related macular degeneration (AMD) represents a leading cause of irreversible blindness in the elderly, primarily by choroidal neovascularization (CNV) leakage. While intravitreal injections of anti-angiogenic antibodies (e.g., aflibercept) provide clinical benefits, their short half-life necessitates frequent administrations, potentially causing ocular infections or retinal detachment. There is an urgent need for effective antibody delivery systems. Mesoporous silica nanoparticles (MSN) have emerged as promising nanocarriers due to their tunable porosity, surface modifiability, and biocompatibility, though their application in ophthalmology for antibody delivery remains underexplored. We developed two MSN carries: spiky mesoporous silica nanospheres (S-MSN) without amino groups and amine-functionalized hollow dendritic mesoporous silica nanospheres (A-HDMSN). Characterization revealed that A-HDMSN exhibited superior properties, including a larger surface area (550.32 vs. 257.72 m²/g), larger mesoporous pore size (17 vs. <10 nm), and 5.28 times higher drug loading capacity (286.31 ± 8.14 vs. 54.26 ± 3.61 μg/mg) compared to S-MSN (n = 3, p < 0.001), attributable to pore size effects and hydrogen bonding. FITC-labeled A-HDMSN demonstrated efficient uptake by retinal pigment epithelial cells (ARPE-19). Notably, A-HDMSN loaded with Aflibercept (A-HDMSN@Afl) showed significant inhibitory effect on VEGF-induced cell migration even 10 days after drug release in vitro, indicating a favorable sustained-release effect of the drug. These findings highlight A-HDMSN as a promising antibody delivery platform that could extend clinical dosing intervals, offering potential for improved AMD management. Full article