J Ocul Pharmacol Ther [JOURNAL]
Sun
200 papers
Optimized Autologous Serum and Activated Leukocyte-Poor Platelet-Rich Plasma Eye Drops Production Protocol: Effect of Fasting, Filtering, and Complement Inactivation on the Concentration of Growth Factors and Lipids.
Sanak F, Iselin K, Kaufmann C … +5 more , Bachmann LM, Buhl D, Parts J, Hedinger YM, Thiel MA
J Ocul Pharmacol Ther · 2026 · PMID 40865098 · Publisher ↗
PURPOSE: To analyze the effect of fasting on volume, growth factor, and lipid concentration in eye drops derived from autologous serum (AS) and leukocyte-poor platelet-rich plasma (LP-PRP). To assess changes in protein a...
PURPOSE: To analyze the effect of fasting on volume, growth factor, and lipid concentration in eye drops derived from autologous serum (AS) and leukocyte-poor platelet-rich plasma (LP-PRP). To assess changes in protein and growth factor concentration after filtration with three different syringe filters and after complement inactivation with heat. METHODS: Blood samples from 10 volunteers after a fasting and nonfasting period were harvested on two separate visits. The total volume gained of AS and LP-PRP was measured. Also, the concentration of lipids, albumin, lysozyme, beta-nerve growth factor (β-NGF), transforming growth factor-β1 (TGF-β1), epidermal growth factor (EGF), hepatocyte growth factor (HGF), platelet-derived growth factor-BB (PDGF-BB), and vascular endothelial growth factor-A (VEGF-A) were quantified in each preparation. The effect of microfiltration was measured in pooled AS and LP-PRP samples before and after filtration with polyethersulfone, polyvinylidene fluoride, or mixed cellulose esters (MCE) membrane syringe filters. The extent of complement inactivation was quantified after incubation at +56°C for 15-240 min. RESULTS: The total volume of AS and LP-PRP and the protein and growth factor concentration remained similar after fasting. Increased triacyl glycerides and similar phospholipid levels were observed in nonfasting samples. Except for a minimal decrease in TGF-β1 after filtration with an MCE membrane filter, filtering did not reduce the concentration of growth factors in AS and LP-PRP. Heat inactivation considerably reduced levels of lysozyme, EGF, HGF, and β-NGF in AS and LP-PRP. CONCLUSIONS: AS should be produced after a fasting period to facilitate the filtration. However, nonfasting does not affect concentrations of relevant biologically active constituents and phospholipids.
Effect of Dasatinib on Oxidative Stress and Neovascularization in Experimental Corneal Neovascularization.
Yildirim H, Balbaba M, Canleblebici M … +5 more , Dal A, Erdağ M, İlhan N, Eröksüz Y, Akdeniz Incili C
J Ocul Pharmacol Ther · 2025 Dec · PMID 40838941 · Publisher ↗
To compare the effects of topical bevacizumab and dasatinib on experimental corneal neovascularization and oxidative stress and to determine the effective dose of dasatinib. Forty-two healthy Wistar-Albino rats were ran...
To compare the effects of topical bevacizumab and dasatinib on experimental corneal neovascularization and oxidative stress and to determine the effective dose of dasatinib. Forty-two healthy Wistar-Albino rats were randomly divided into six groups. The right corneas of all rats except group 1 were cauterized with silver nitrate. Group 2 received dimethyl sulfoxide, group 3 received topical bevacizumab (5 mg/mL, three times a day), and groups 4, 5, and 6 received dasatinib (2.5 mg/dL, 5 mg/dL, and 10 mg/dL, three times a day respectively), between days 1 and 7. The corneas were removed to determine the level of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) values for neovascularization and superoxide dismutase (SOD), malondialdehyde (MDA), and protein carbonyl (PC) levels for analyzing oxidative stress. Nonparametric variance analysis and post hoc Tamhane test was used for statistical analysis. The VEGF level was statistically significantly lower in groups 3, 4, and 5 compared with group 2 ( < 0.05). The PDGF, SOD and MDA levels were compared; there was significant difference between all the groups compared with group 2. However, the MDA level for group 6, compared with other treatment groups, had a higher value ( < 0.05). The PC levels compared were statistically significantly lower in groups 3 and 4 compared with group 2 ( < 0.05). Dasatinib 2.5 mg/dL was as effective as bevacizumab and seems to be dose-dependent and higher doses than 2.5 mg/dL show higher oxidative stress and an increase in neovascularization.
The Endocannabinoid System: Role in Ocular Physiology and Therapeutic Potential in Eye Diseases: A Narrative Review.
Feki O, Zhioua-Braham I, Haddar S … +3 more , Arfaoui A, Errais K, Feki M
J Ocul Pharmacol Ther · 2025 Nov · PMID 40838892 · Publisher ↗
The endocannabinoid system (ECS) is a multicomponent signaling network that controls several physiological processes, including neurological, immune, cardiovascular, digestive, and ocular functions. The components of ECS...
The endocannabinoid system (ECS) is a multicomponent signaling network that controls several physiological processes, including neurological, immune, cardiovascular, digestive, and ocular functions. The components of ECS (i.e., receptors, ligands, metabolizing enzymes, and carriers) are expressed in eye structures and neurological areas involved in the visual process. Experimental evidence supports ECS involvement in ocular pathophysiology. Preclinical and clinical studies indicate that cannabinoids (CBs) lower intraocular pressure and exert vasoactive, anti-inflammatory, and protective effects in the retina and ocular surface. However, CBs elicit modest and transient effects while inducing tolerance, dependence, and adverse effects, which prevent their use in ophthalmic clinics. This review summarizes experimental and clinical data on the role of ECS in ocular pathophysiology. It also reports research on the therapeutic potential of CBs in common eye disorders. Lastly, it highlights promising alternative strategies for modulating ECS and improving ocular drug delivery to improve therapeutic efficiency in ophthalmic clinics.
Effect of Topical Application of Dexamethasone on CC Chemokine Receptor 3 Expression in Human Pterygium.
Wu J, Wu H, Zhou B … +5 more , He X, Kang Z, Chen T, Liu G, Lu P
J Ocul Pharmacol Ther · 2025 Nov · PMID 40833917 · Publisher ↗
To evaluate the effects of preoperative topical demethasone on CC chemokine receptor 3 (CCR3) expression in human pterygium. Forty cases of patients with pterygium were divided into a dexamethasone group and a control g...
To evaluate the effects of preoperative topical demethasone on CC chemokine receptor 3 (CCR3) expression in human pterygium. Forty cases of patients with pterygium were divided into a dexamethasone group and a control group, which were treated topically with 3 g/L tobramycin + dexamethasone or 3 g/L tobramycin eye drops in the surgical eyes 2 weeks before surgery. Pterygium samples were collected from the subjects after pterygium excision surgery and processed for real-time polymerase chain reaction and Western blot to examine CCR3 expression. The effects of CCR3 signaling on tube-forming properties and proliferation of human retinal vascular endothelial cells (HRECs) were investigated using a Matrigel assay and a cell counting kit (CCK)-8 assay. The effects of CCR3 signaling on the proliferation and migration of human keloid fibroblasts (HKFs) were investigated using the CCK-8 assay and wound-healing assay. CCR3 mRNA and protein were detected in pterygium. CCR3 expression levels were reduced in the dexamethasone group compared with the control group ( < 0.05). CCR3 expression levels were associated with basic fibroblast growth factor and inducible nitric oxide synthase expression levels in pterygium. experiments showed that CCR3 signaling increased the number of intact capillary tubes and promoted the proliferation of HRECs. In addition, CCR3 signaling increased the proliferation and migration of HKFs. CCR3 signaling may play an important role in the pathogenesis of pterygium. The proangiogenic and profibrotic functions of CCR3 signaling may be by promoting tube formation and proliferation of vascular endothelial cells and promoting proliferation and migration of fibroblasts.
Rosmarinic Acid Mitigates Lipopolysaccharide-Induced Inflammation and Oxidative Stress in Human Corneal Epithelial Cells as an Keratitis Cell Model.
Shen M, Xu B
J Ocul Pharmacol Ther · 2025 Dec · PMID 40824765 · Publisher ↗
Inflammation and oxidative stress are principal contributors to the pathogenesis of numerous ocular conditions, including keratitis. Lipopolysaccharide (LPS)-induced corneal inflammation is a commonly used model to expl...
Inflammation and oxidative stress are principal contributors to the pathogenesis of numerous ocular conditions, including keratitis. Lipopolysaccharide (LPS)-induced corneal inflammation is a commonly used model to explore the anti-inflammatory and antioxidant potential of novel therapeutic agents. Human corneal epithelial cells (HCECs) were stimulated with LPS to reproduce an inflammatory microenvironment. Rosmarinic acid was administered at different concentrations, and its effects were evaluated using several endpoints. Cell viability was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Intracellular reactive oxygen species (ROS), pro-inflammatory cytokines (interleukin [IL]-6, IL-1β, tumor necrosis factor-α [TNF-α]), transforming growth factor-β (TGF-β), and nuclear factor erythroid 2-related factor 2 (Nrf2) and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were quantified at mRNA and protein levels. Rosmarinic acid significantly restored cell viability, reduced ROS generation, and suppressed pro-inflammatory cytokine expression in a concentration-dependent manner. Furthermore, it modulated TGF-β expression and normalized NF-κB and Nrf2 levels suggesting a broader regulatory effect on inflammatory and repair mechanisms. These findings underscore the potent anti-inflammatory and antioxidative properties of rosmarinic acid in HCECs. Rosmarinic acid may represent a promising therapeutic avenue for the management of corneal inflammation and oxidative stress-induced ocular pathologies.
Custom-Made Injector for Suprachoroidal Ocular Delivery: Effect of Intraocular Pressure, Volume, and Location on the Distribution of Aqueous Solutions in Rabbits.
Nork TM, Katz AW, Rasmussen CA … +3 more , Kim CBY, Sonnentag PJ, Murphy CJ
J Ocul Pharmacol Ther · 2025 Nov · PMID 40780836 · Full text
Develop a custom-made injector system for delivery of aqueous solutions to the suprachoroidal space (SCS). And to test the effect of intraocular pressure (IOP), volume, and location on distribution. SCS injectors were p...
Develop a custom-made injector system for delivery of aqueous solutions to the suprachoroidal space (SCS). And to test the effect of intraocular pressure (IOP), volume, and location on distribution. SCS injectors were produced in the laboratory using readily available components. Fifty 100 µL of either fluorescein sodium and/or indocyanine green (ICG) dye solutions were injected 6-mm posterior to the corneal limbus in either the superotemporal or inferonasal quadrants of the eyes of albino rabbits. Coverage of the injected dyes was documented . Distribution of 50- and 100-µL single-injection volumes was compared, as were 50-µL injections in two opposing quadrants. The vasoconstrictor endothelin-1 was injected into some eyes as a test of efficacy. To determine the possible effects of IOP on injection coverage, both eyes of 6 rabbits were injected with ICG in a crossover design with the IOPs of the eyes held manometrically at either 10 or 35 mmHg. Successful SCS injections, as determined by fundus imaging, were done in more than 40 rabbit eyes [as well as 40 nonhuman primate eyes in separate studies]. One hundred microliters single injections provided better coverage than 50 µL, but the most complete coverage was with two 50-µL injections in opposite quadrants, although gaps remained. No statistically significant difference in coverage between IOPs of 10 and 35 mmHg was observed. Construction of a reliable custom-made injector system is feasible. IOP at the pressures measured did not appear to affect coverage of the suprachoroidally injected ICG dye solution.
Comparison of Topical Gatifloxacin and Levofloxacin at Different Durations in Eliminating Conjunctival Bacterial Flora.
Lei J, Zeng L, Gao X … +2 more , Wang D, Li H
J Ocul Pharmacol Ther · 2025 Dec · PMID 40765510 · Publisher ↗
To compare the efficacy of topical levofloxacin and gatifloxacin at different durations in reducing conjunctival bacteria. In total, 285 patients (290 eyes) scheduled to undergo ophthalmic surgery were divided into 6 gr...
To compare the efficacy of topical levofloxacin and gatifloxacin at different durations in reducing conjunctival bacteria. In total, 285 patients (290 eyes) scheduled to undergo ophthalmic surgery were divided into 6 groups to receive either gatifloxacin or levofloxacin eye drops for 1 day (12 times/day), 2 days (6 times/day), or 3 days (4 times/day) before surgery. Conjunctival sac specimens were collected from all patients before treatment (T0) and after treatment (T1). All specimens were inoculated onto Columbia blood agar plates. Before treatment, the culture positivity rate was 50.34% for 290 samples, and after treatment, the culture positivity rate was 11.72% ( < 0.05). spp. and spp. were the most predominantly detected microbial groups before and after treatment. The bacterial eradication rate was higher in the gatifloxacin group (87.01%) than in the levofloxacin group (81.15%). There was no difference in culture positivity between gatifloxacin 1-, 2-, and 3-day groups ( > 0.05). The culture positivity rate was significantly higher in the levofloxacin 1-day group than in the 2- and 3-day groups ( < 0.05). Both drugs were effective in removing gram-positive bacillus at different durations ( < 0.01), but only the levofloxacin treatment for 3 days significantly reduced the positive cultures of gram-positive cocci in the conjunctival sac ( < 0.05). Our study demonstrated that preoperative use of levofloxacin to prevent infection takes at least 2-3 days, and 1 day is a sufficient duration for topical gatifloxacin to significantly reduce conjunctival bacterial flora.
Nonsurgical Therapies for Preventing Corneal Scarring: A Systematic Review of the Past Decade.
Xia R, Lin L, Liu Z … +1 more , Chen W
J Ocul Pharmacol Ther · 2025 Dec · PMID 40765328 · Publisher ↗
Corneal scarring remains a leading cause of visual impairment and preventable blindness worldwide, particularly where access to corneal transplantation is limited. Over the past decade, significant advances have been mad...
Corneal scarring remains a leading cause of visual impairment and preventable blindness worldwide, particularly where access to corneal transplantation is limited. Over the past decade, significant advances have been made in nonsurgical therapies aimed at preventing or mitigating corneal fibrosis. This systematic review summarizes emerging nonsurgical interventions, including synthetic drugs, plant- and animal-derived bioactives, biologics, cell-based therapies, and gene therapies. A paradigm shift has occurred from nonspecific anti-inflammatory agents toward therapies targeting fibrotic-related pathways (e.g., transforming growth factor-β, Rho-associated protein kinase, extracellular matrix remodeling), with growing emphasis on regenerative strategies such as exosome treatments and gene modulation. Despite promising preclinical data, major translational challenges remain, including delivery optimization, scalability, and regulatory hurdles. Standardizing outcome measures across models and exploring combination therapies targeting multiple fibrotic pathways represent critical future directions. Continued research to validate the efficacy and safety of these emerging interventions is essential to expand therapeutic options and enhance vision restoration efforts globally.
Beyond the Prostate: A Visionary Study on Ocular Impacts of Benign Prostatic Hyperplasia Drugs.
Khan H, Aftab OM, Billah MS … +1 more , Khouri AS
J Ocul Pharmacol Ther · 2025 Oct · PMID 40764034 · Publisher ↗
Benign prostatic hyperplasia (BPH) medications have been demonstrated in the literature to cause specific iris adverse effects. We conducted a comprehensive analysis of adverse ocular effects across various pathologies u...
Benign prostatic hyperplasia (BPH) medications have been demonstrated in the literature to cause specific iris adverse effects. We conducted a comprehensive analysis of adverse ocular effects across various pathologies using the FDA Adverse Event Reporting System (FAERS). The FAERS pharmacovigilance database was scrutinized for ocular adverse events tied to BPH medications. With 23,440 reports linked to BPH medications and 11,416,316 unrelated reports, the disproportionality analysis utilized proportional reporting ratio, reporting odds ratio, empirical Bayes geometric mean, and information component. Investigating the correlation between ocular adverse events and widely used BPH medications in the FAERS database aids in identifying noteworthy drug safety signals through positive values across all detection algorithms. We identified 11,439,756 unique adverse event reports in the FDA FAERS database (2004-2023Q3). Of these, 1,682 were associated with examined BPH medications. Tamsulosin constituted the majority with 1,356 reports (80.67%), followed by finasteride with 180 reports (10.71%). Predominant categories included iris and cataract symptoms (51.78%), visual and neurological changes (29.90%), and changes in the retina (8.86%). Notably, iridocele, macular fibrosis, corneal changes (like blepharitis), lacrimal gland changes, retinal degeneration/detachment, vitreous floaters, and retinal edema exhibited significant safety signals in both tamsulosin and finasteride, the primary contributors to reports. Significant drug safety signals in FAERS disproportionality analysis underscore the necessity for deeper exploration of the link between BPH medications and serious ocular adverse effects, including macular fibrosis, corneal pathologies, lacrimal gland changes, and macular edema.
The Efficacy and Safety of Tumor Necrosis Factor Alpha Inhibitors in the Treatment of Noninfectious Uveitis: A Systematic Review and Meta-Analysis.
Wang Z, Li G, Lu H … +1 more , Wang J
J Ocul Pharmacol Ther · 2025 Nov · PMID 40762072 · Publisher ↗
This study assessed the comparative efficacy and safety of tumor necrosis factor alpha (TNF-α) inhibitors in treating noninfectious uveitis (NIU). A comprehensive search was performed in PubMed, Embase, Cochrane Library...
This study assessed the comparative efficacy and safety of tumor necrosis factor alpha (TNF-α) inhibitors in treating noninfectious uveitis (NIU). A comprehensive search was performed in PubMed, Embase, Cochrane Library, ClinicalTrials.gov, China National Knowledge Infrastructure, and Wanfang Database from January 2010 to March 2024. The outcomes measured included inflammation improvement, visual acuity (VA) improvement, corticosteroid (CS)-sparing effect, central macular thickness (CMT) reduction, and adverse event incidence. Meta-analyses were conducted using RevMan 5.4 and Stata 16 software. A total of 40 studies were included, involving 3,250 patients. TNF-α inhibitors showed a 90.4% inflammation improvement rate [95% confidence interval (CI): 0.770-0.987], 35.2% VA improvement (95% CI: 0.152-0.553), 55.3% CS-sparing effect (95% CI: 0.297-0.796), and CMT reduction of 62.37 µm (95% CI: 45.41-79.32 µm). Adverse events occurred in 24.0% of patients (95% CI: 0.170-0.310). No significant differences were observed between adalimumab and infliximab in inflammation improvement ( = 0.60) or CMT reduction ( = 0.55), but infliximab had higher adverse event rates ( = 0.0001; relative risk = 1.71, 95% CI: 1.30-2.24). This meta-analysis demonstrates that TNF-α inhibitors significantly improve inflammation, VA, and reduce CMT and CS use in NIU. While adalimumab and infliximab exhibit comparable efficacy, infliximab is associated with a higher adverse event rate, highlighting the need for personalized treatment.
Physicochemical Properties and Rheological Behavior of Artificial Tears for Dry Eye Syndrome.
Montmeat D, Thouvenin A, Rasamison R … +1 more , Boudy V
J Ocul Pharmacol Ther · 2025 Dec · PMID 40762066 · Publisher ↗
Dry eye syndrome (DES) is a growing global public health problem. The clinical management of DES involves general advice on environmental and lifestyle adaptations, as well as the use of artificial tears. While there are...
Dry eye syndrome (DES) is a growing global public health problem. The clinical management of DES involves general advice on environmental and lifestyle adaptations, as well as the use of artificial tears. While there are a multitude of tear substitutes and eye drops for DES on the market, with a wide variety of ingredients, there are no specific recommendations on the priority use of one or the other. The aim of this study was to determine and compare physicochemical and rheological properties of ten widely used eye drops for DES, pure or mixed in tears to get closer to the real conditions of use. Physicochemical characterization was done according to pH, density and osmolarity. Rheological characterization was done according to flow measurements and oscillatory measurements. Three categories of eye drops could be identified according to their rheological behavior: those with significant shear-thinning behavior, those with moderate shear-thinning behavior, and those with Newtonian behavior. Some changed their rheological behavior when mixed with simulated tear fluid. Within each category, differences were identified based on physicochemical criteria or the presence of problematic excipients such as preservatives or phosphates. This categorization could be used to refine prescriptions, particularly when several eye drops are to be combined, in order to avoid redundancy of mechanism of action.
Infectious, Immune-Mediated, and Vaccine-Associated Ocular Adverse Events.
Rojas R, Hinkle DM
J Ocul Pharmacol Ther · 2025 Oct · PMID 40737188 · Publisher ↗
Abstract loading — click title to view on PubMed.
Assessment of Bacterial and Fungal Contamination in Preservative-Free Multi-Dose Cyclosporine Eye Drops.
Sarmis A, Yilmaz OF, Mutlu MA … +3 more , Karaca S, Turan D, Oguz H
J Ocul Pharmacol Ther · 2025 Oct · PMID 40735974 · Publisher ↗
This study investigated the bacterial and fungal contamination of preservative-free, multidose cyclosporine (PFMD-Cyc) bottles. One hundred PFMD-Cyc eye drops administered by different patients for a minimum of 3 weeks...
This study investigated the bacterial and fungal contamination of preservative-free, multidose cyclosporine (PFMD-Cyc) bottles. One hundred PFMD-Cyc eye drops administered by different patients for a minimum of 3 weeks were analyzed. The caps and first and second drops from the bottles underwent microbiological testing using sheep blood agar, chocolate agar, Sabouraud dextrose agar, and broth media. Conjunctival cultures were obtained from patients whose bottles were contaminated. The residual drug inside the contaminated bottles was examined by drilling the bottles' underside. Microbial contamination was detected in 47% ( = 47) of the samples, with both poly- and monomicrobial growth. Fifty-nine species (25 gram-positive and 11 gram-negative bacteria, 15 yeasts, and 8 molds) were identified in the contaminated bottles. The most prevalent microorganisms were ( = 11), ( = 7), and spp. ( = 4). Conjunctival cultures from 4 patients revealed the same pathogens identified in the contaminated bottle, including and . In addition to bacteria, a particularly high level of fungal contamination was detected. Conjunctival microorganisms were also detected in select samples. Patients should be advised to practice proper hand hygiene before administering eye drops. Moreover, meticulous attention to the storage conditions of medications during treatment is essential. Furthermore, research into fungal contamination of ophthalmical solutions, particularly immunosuppressive eye drops, is warranted.
Evaluation of Systemic Exposure to Intracameral Tropicamide 0.02%, Phenylephrine 0.31%, and Lidocaine 1% in Pediatric Cataract Surgery.
Herbots H, Van Os L, Aerts W … +4 more , Tassignon MJ, Covaci A, Dumitrascu C, Saldien V
J Ocul Pharmacol Ther · 2025 Oct · PMID 40681312 · Publisher ↗
Pediatric cataract surgery requires mydriasis, typically achieved with eye drops. An intracameral mydriatic combining tropicamide 0.02%, phenylephrine 0.31%, and lidocaine 1% is established in adults, but not in children...
Pediatric cataract surgery requires mydriasis, typically achieved with eye drops. An intracameral mydriatic combining tropicamide 0.02%, phenylephrine 0.31%, and lidocaine 1% is established in adults, but not in children. We aimed to evaluate the safety profile of this intracameral mydriatic in children. We conducted a prospective observational cohort study on 40 patients, aged 8 weeks to 17 years, undergoing cataract surgery under general anesthesia (GA) and receiving 1 intracameral injection (0.1 mL) of the mydriatic. Thirteen patients underwent immediate sequential bilateral cataract surgery with a second injection to the second eye. We evaluated the incidence of hemodynamic adverse effects and assessed systemic exposure by quantification of plasma concentrations of phenylephrine and tropicamide at 4 fixed time points during the procedure. The highest plasma concentrations of phenylephrine and tropicamide were detected in the youngest patients (age 8 weeks-1 year), with a significant increase from baseline ( = 0.008 and = 0.023, respectively). In patients aged 1-6 years, significant changes were observed only in the plasma concentration of phenylephrine ( < 0.001). For patients aged 6-17 years, there was no significant rise in phenylephrine nor in tropicamide plasma concentration ( = 0.194 and = 1.000). No clinically important changes in hemodynamic parameters occurred in any age group. Sequential bilateral administration did not result in an increase in plasma concentrations, nor in an increase of hemodynamic adverse effects. Intracameral mydriatic injection did not induce cardiovascular adverse events, and systemic exposure was minimal in this pediatric population undergoing cataract surgery under GA.
GCN5-TFEB Pathway Regulates Inflammation by Tuning Autophagic Degradation of Retinoic Acid-Induced Gene-I in Human Conjunctival Epithelial Cells.
Zhou J, Wang D, Li GC … +5 more , Huang Q, Wang L, Huang W, Xiang Z, Fan Y
J Ocul Pharmacol Ther · 2025 Dec · PMID 40632010 · Publisher ↗
To evaluate the pathological role of the GCN5-TFEB axis in dry eye diseases (DEDs) by detecting the autophagic degradation of retinoic acid-inducible gene I (RIG-I), a master RNA-sensing receptor in cells. RNA-sequencin...
To evaluate the pathological role of the GCN5-TFEB axis in dry eye diseases (DEDs) by detecting the autophagic degradation of retinoic acid-inducible gene I (RIG-I), a master RNA-sensing receptor in cells. RNA-sequencing analysis and quantitative PCR (qPCR) analysis of the expression level of genes related to the interferon (IFN)-I signaling pathway was used to evaluate the inflammatory level of cells overexpressed with General control non-repressed protein 5 (GCN5) or empty vector, which were further confirmed by Western Blot (WB) analysis. siRNA and chemical treatment were used to inhibit GCN5. The acetylation level of transcription factor EB (TFEB) was detected by WB, and qPCR analysis confirmed the transcriptional activity of TFEB. Immunofluorescence and WB were used to measure autophagy and lysosomal biogenesis. When the GCN5 activity was regulated, the autophagic degradation of RIG-I and its pathological role in DEDs were determined by detecting the protein level of RIG-I and the level of cell inflammation. Cells that overexpressed GCN5 showed increased expression of genes involved in the IFN-I signaling pathway compared with cells transfected with an empty vector. Inhibition of GCN5 decreased the acetylation level of TFEB and increased the transcriptional activity of TFEB, combined with the elevated autophagy and lysosomal biogenesis in human corneal epithelial cells (HCECs). Promoting the autophagic degradation of RIG-I by GCN5 inhibition could alleviate the IFN-I signaling pathway. GCN5 could aggravate the activity of the IFN-I signaling pathway in HCECs by acetylating TFEB and inhibiting autophagy, which caused the accumulation of RIG-I. This process could be used to control the overactivation of inflammation in the pathological development of DED.
Minichromosome Maintenance Complex Genes Are Candidate Biomarkers of Retinal Degeneration.
Sun N, Hu X, Wang J … +2 more , Yao T, Wang Z
J Ocul Pharmacol Ther · 2025 Oct · PMID 40576728 · Publisher ↗
Retinal degeneration is the primary cause of blindness and is characterized by progressive dysfunction and death of retinal cells, leading to irreversible vision impairment. As far as is known, there are currently no eff...
Retinal degeneration is the primary cause of blindness and is characterized by progressive dysfunction and death of retinal cells, leading to irreversible vision impairment. As far as is known, there are currently no effective treatments for this condition. The identification of novel therapeutic targets remains a critical challenge. To address this vital issue, we performed an in-depth transcriptome analysis of the sodium iodate-induced cell model (NaIO-treated cells), further identified the differential gene expression and common pathways, performed enrichment analysis, constructed protein-protein interaction (PPI) networks, and screened for three core DNA replication-related genes (, , and ). Subsequently, quantitative real-time polymerase chain reaction (qPCR) and immunohistochemistry assays were performed to verify the expression levels of hub genes in the NaIO-treated adult retinal pigment epithelial cell line-19 and animal models. The pathways were mainly focused on DNA replication in the enrichment analysis. PPI network analysis revealed that minichromosome maintenance complex genes associated with DNA replication were core genes for retinal degeneration. qPCR and immunohistochemistry assays showed that the expression levels of hub genes were downregulated in the NaIO-treated cell and animal models. Collectively, our bioinformatics analysis, coupled with experimental validation, identified three core DNA replication-related genes (, , and ) with potential implications in retinal degeneration, suggesting their roles in the disease process. These findings shed light on the molecular underpinnings of retinal degeneration and pave the way for the development of targeted therapies aimed at modulating DNA replication-related gene activity to treat retinal degeneration.
Exploring the Efficacy of AZD6738 in Corneal Neovascularization: Autophagy Enhancement and Angiogenesis Inhibition.
Wang Q, Peng Y, Wang S … +8 more , Xu J, Cheng C, Luo X, Yu K, Yao W, Pi Y, Zhu Z, Yu Y
J Ocul Pharmacol Ther · 2025 Oct · PMID 40576624 · Publisher ↗
This study aimed to investigate the therapeutic potential of AZD6738, an ataxia-telangiectasia and rad3-related (ATR) kinase inhibitor, in preventing corneal neovascularization (CNV) by exploring its effects on autophagy...
This study aimed to investigate the therapeutic potential of AZD6738, an ataxia-telangiectasia and rad3-related (ATR) kinase inhibitor, in preventing corneal neovascularization (CNV) by exploring its effects on autophagy regulation and angiogenesis. Human umbilical vein endothelial cells were cultured and treated with varying concentrations of AZD6738 and vascular endothelial growth factor (VEGF) to assess cell viability, migration, and tube formation. A corneal alkali burn model in Sprague-Dawley rats was established to evaluate the effects of AZD6738 on CNV. Autophagy was assessed using monodansylcadaverine (MDC) staining, western blotting, and qRT-PCR to measure the expression of autophagy-related markers and key proteins involved in the PI3K-AKT pathway. Immunohistochemistry and immunofluorescence staining were employed to examine histological changes and the expression of markers related to neovascularization and fibrosis. The study demonstrated that AZD6738 significantly inhibited cell viability in a dose-dependent manner. AZD6738 effectively reduced VEGF-induced cell migration and tube formation. Moreover, the introduction of AZD6738 enhanced autophagy, as indicated by increased MDC staining, upregulated Beclin1 expression, and an elevated LC3 II/I ratio. The inhibitor also suppressed the PI3K-AKT pathway, reducing VEGF and VEGFR2 expression, and decreasing the phosphorylation levels of AMPK and AKT. In an experimental CNV model, AZD6738 treatment resulted in a significant reduction in CNV, with fewer and shorter blood vessels observed, as well as changes in autophagy-related proteins. AZD6738 showed potential in preventing CNV. Its ability to enhance autophagy and inhibit PI3K-AKT-VEGF pathways in angiogenesis suggests that AZD6738 could be an effective treatment strategy for CNV.
Eyes on New Product Development.
Novack GD
J Ocul Pharmacol Ther · 2025 Aug · PMID 40552374 · Publisher ↗
Abstract loading — click title to view on PubMed.
Mucoadhesive Silk Fibroin Nanoparticles for Drug Delivery to the Ocular Surface.
Srikajorn C, Tiyaboonchai W, Srinivas SP … +1 more , Thongsuk W
J Ocul Pharmacol Ther · 2025 Sep · PMID 40552360 · Publisher ↗
To develop silk fibroin nanoparticles (SFNs) for prolonged drug delivery to the ocular surface. SFNs were prepared using nanoprecipitation, coated with chitosan (CS; positively charged), and stabilized with polyethylene...
To develop silk fibroin nanoparticles (SFNs) for prolonged drug delivery to the ocular surface. SFNs were prepared using nanoprecipitation, coated with chitosan (CS; positively charged), and stabilized with polyethylene glycol 400. Their morphology, particle size distribution, and surface charge were analyzed using dynamic light scattering. Fourier transform infrared (FTIR) spectroscopy assessed the intermolecular interactions between CS and silk fibroin. The entrapment efficiencies (EE) for sodium fluorescein (NaF) and Nile Red (NR), which served as hydrophilic and hydrophobic drug surrogates, respectively, were determined. The mucoadhesiveness of SFNs was examined with freshly isolated porcine eyes. Cellular uptake and cytotoxicity were evaluated in a human corneal epithelium cell line (HCEC). SFNs were spherical, measuring 198.47 ± 35.54 nm in diameter, and had a surface charge of 38.33 ± 0.67 mV. The coating of CS on SFNs resulted in a peak shift in the amide group in the FTIR spectrum. The maximum EEs for NaF and NR in SFNs were approximately 95% and 67%, respectively. SFNs exhibited prolonged mucoadhesion on corneas for over 240 min and were rapidly endocytosed by HCEC in less than 30 min without inducing cytotoxicity. The properties of SFNs are suitable for delivering drugs to the ocular surface.
Tear Pharmacokinetics and Systemic Exposure of Dexamethasone Canalicular Inserts in Rabbits.
Moon M, Won J, Kang W
J Ocul Pharmacol Ther · 2025 Oct · PMID 40551412 · Publisher ↗
A dexamethasone canalicular insert, Dextenza®, has been used to treat anterior inflammation of the eye, including keratoconjunctivitis sicca. This study aimed to investigate the tear pharmacokinetics and systemic exposur...
A dexamethasone canalicular insert, Dextenza®, has been used to treat anterior inflammation of the eye, including keratoconjunctivitis sicca. This study aimed to investigate the tear pharmacokinetics and systemic exposure of dexamethasone in New Zealand White rabbits after inserting the preparation into the punctum and to correlate the data with the dissolution test. Dextenza was inserted into the punctum of rabbits. A paper strip serially collected tears, and dexamethasone concentrations in tears and plasma were measured using HPLC-MS/MS. The time courses of tear and plasma dexamethasone concentrations were characterized. The release of dexamethasone from the insert to tears in rabbits was completed in ∼ 5 days, much faster than in humans and dogs (30 days). The time course of plasma dexamethasone concentration was fully characterized, in contrast to the fact that systemic exposure was merely observed in the other species. The present results might be attributed to the anatomical structure of the lacrimal sac beneath rabbits' canaliculi. The dissolution pattern represented an excellent correlation with the release in tears. We first examined the pharmacokinetic study of the canalicular insert in rabbits, which could be applied to the other insert studies in the species.
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