Tear film disorders, particularly dry eye disease (DED), are among the most common ocular surface conditions and arise from dysfunction of the lacrimal functional unit, including the lacrimal gland, meibomian glands, and...Tear film disorders, particularly dry eye disease (DED), are among the most common ocular surface conditions and arise from dysfunction of the lacrimal functional unit, including the lacrimal gland, meibomian glands, and conjunctival goblet cells.Despite the recent advancements in the management of the tear film disorders, the treatment still remains palliative. Hence there is a need for research focusing on regenerative approaches to restore the physiological functions and homeostasis of the tear film. A selective literature review was performed using PubMed, Google Scholar, and Medline. The review is based on 127 relevant publications published up to January 2026, with emphasis on experimental and translational approaches for restoring tear film homeostasis. In addition, the latest advances in lacrimal gland regeneration are described, including recent studies conducted by our research group. This review aims to first give an overview about the underlying diseases which alters the tear film composition, secondly highlighting the current treatment methods and their limitation and finally analyze recent experimental strategies that promotes tear film regeneration including stem cell-based therapies, tissue engineering of the lacrimal gland, neurotrophic factor supplementation, gene therapy, and biomaterial-assisted delivery systems. Regenerative approaches for tear film disorders are evolving from symptomatic management toward restoration of functional tissue. Although most strategies remain in preclinical or early translational stages, advances in stem cell biology, biomaterials, secretome research, and tissue engineering provide a promising foundation for future therapies targeting the lacrimal functional unit and long-term tear film homeostasis. By summarizing current findings and identifying research gaps, this review can highlight promising approaches for translational research and potential clinical applications.
Chen X, Wu G, Wu X
… +8 more, Jin Y, Zhu H, Liu J, Liu M, Liao S, Li F, Fang X, Meng Q
Curr Eye Res
· 2026 Jun · PMID 42366514
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PURPOSE: The aim of this study was to investigate the function of Apolipoprotein C3 (APOC3) in the retina under hypoxic conditions. METHODS: The quantitative expression of APOC3 in the aqueous humor of patients with diab...PURPOSE: The aim of this study was to investigate the function of Apolipoprotein C3 (APOC3) in the retina under hypoxic conditions. METHODS: The quantitative expression of APOC3 in the aqueous humor of patients with diabetic retinopathy (DR) was determined using proteomics datasets. A multiplex immunoassay was used to measure APOC3 levels in the serum of patients with DR. Western blotting and enzyme-linked immunosorbent assays were used to assess APOC3 expression in the liver, duodenum, retina, and serum of db/db mice and oxygen-induced retinopathy (OIR) mice, as well as in human retinal microvascular endothelial cells (hRMECs) exposed to high glucose, hypoxia, or both. Cell proliferation, migration, and tube formation assays were conducted in hRMECs treated with recombinant APOC3 (r-APOC3), hypoxia, or both. RNA sequencing and inhibition assays were performed to explore the pathways associated with r-APOC3 and hypoxia stimulation. RESULTS: APOC3 expression was significantly increased in the aqueous humor and serum of patients with DR, as well as in the liver, duodenum, serum, and retina of db/db and OIR mice, but did not change markedly in either the hRMECs or their conditioned media under given conditions. r-APOC3 combined with hypoxia significantly enhanced the proliferation, migration, and tube formation of hRMECs, promoting the upregulation of MYC, VEGFA, and IL6. Inhibition of MYC expression reduced VEGFA and IL6 levels and alleviated the phenotypic changes in hRMECs treated with r-APOC3 and hypoxia. CONCLUSION: APOC3 may promote retinal angiogenesis activation of the MYC pathway under hypoxic conditions, suggesting its involvement in DR.
Xue Z, Zhang R, Zhang Q
… +5 more, Chen ZJ, Zhang Y, Qu J, Su J, Yuan J
Curr Eye Res
· 2026 Jun · PMID 42345359
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PURPOSE: To evaluate whether thyroid-related medication-taking traits show evidence consistent with a possible causal relationship for diabetic retinopathy (DR). METHODS: We utilized genome-wide association study (GWAS)...PURPOSE: To evaluate whether thyroid-related medication-taking traits show evidence consistent with a possible causal relationship for diabetic retinopathy (DR). METHODS: We utilized genome-wide association study (GWAS) summary statistics from UK Biobank, which included 23 medication-taking traits in a sample of approximately 320,000 individuals and DR data from 1,652 cases and 60,577 controls. We employed Mendelian randomization (MR) approach to investigate the possible causal relationships between medication-taking characteristics and DR. Possible causal effects were screened with TwoSampleMR inverse-variance weighting, confirmed by univariable MR after pleiotropic SNPs were removed MR-PRESSO; reverse MR excluded reverse causality, and public GWAS data verified the thyroid-disease associations. RESULTS: We found drugs used in diabetes and thyroid preparations showed a significant association with DR ( < 0.05/22). After removing pleiotropic SNPs, the UVMR analysis suggested a potential relationship between thyroid preparations and DR (IVW: OR = 1.18, = 1.91 × 10). Furthermore, the MR analysis indicated that both hypothyroidism and hyperthyroidism were associated with a significantly higher risk of DR (OR = 1.31, = 1.75 × 10; OR = 1.32, = 1.05 × 10). The findings from different single-nucleotide analytic methods were consistent, suggesting the robustness of the possible causal associations. CONCLUSIONS: Our findings suggest thyroid dysfunction appears to causally elevate DR risk, informing screening and prevention in diabetes. The precise mechanisms may involve thyroid-related oxidative stress and inflammation.
Curr Eye Res
· 2026 Jun · PMID 42345322
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PURPOSE: To explore the reasons for the mechanical changes of the lens capsule after indocyanine green (ICG) staining through microstructure alterations. METHODS: A total of 40 anterior capsules were obtained during cata...PURPOSE: To explore the reasons for the mechanical changes of the lens capsule after indocyanine green (ICG) staining through microstructure alterations. METHODS: A total of 40 anterior capsules were obtained during cataract surgery. Two bands of the same size were prepared for each capsule. One was stained with ICG for 10 s (Group 1) or 1 min (Group 2), and the other was used as a control. The mechanical property measurement was carried out using a nanoindentation instrument. The other anterior capsules were subjected to ultrastructural analysis using scanning electron microscopy and transmission electron microscopy. RESULTS: The average elastic modulus and the average hardness of capsule fragments in Group 1 had no significant change after staining. There were significant differences in the average elastic modulus (4.48 ± 0.75 GPa vs.4.08 ± 0.49 GPa, = 0.04) and average hardness (0.19 ± 0.03 GPa vs.0.15 ± 0.02 GPa, = 0.01) of capsule fragments after staining in Group 2. Electron microscope observation showed that the cells were swollen, the mitochondrial outer membrane was broken, part of the endoplasmic reticulum was vacuolized, the surface fibers of the capsule were disordered, and the fiber structures were fused and rigid after ICG staining. CONCLUSIONS: ICG staining significantly affects the mechanical properties and ultrastructure of the human lens capsule. The alteration of the fiber structure on the surface of the capsule might be the cause of the mechanical changes in the capsule.
Maity M, Siddiqui MG, Singh V
… +2 more, Basu S, Singh S
Curr Eye Res
· 2026 Jun · PMID 42333594
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PURPOSE: The current study evaluated the structure and function of corneal nerves in symptomatic versus asymptomatic visual display terminal (VDT) users, along with tear neuropeptides. METHODS: A cross-sectional, single-...PURPOSE: The current study evaluated the structure and function of corneal nerves in symptomatic versus asymptomatic visual display terminal (VDT) users, along with tear neuropeptides. METHODS: A cross-sectional, single-masked study divided VDT users into symptomatic ( = 51; ocular surface disease index (OSDI) > 13, tear osmolarity, noninvasive tear break-up time (NIBUT) < 10 s, and positive corneal staining) and asymptomatic groups ( = 21, OSDI ≤ 13, NIBUT > 10 s). Participants underwent detailed tear film examination (Oculus keratograph 5M), blink rate, corneal sensitivity (Cochet-Bonnet aesthesiometer), and confocal microscopy (IVCM, HRT II-RCM) testing. ELISA of tear cytokines (IL1a, TNFa, IL6, MMP 9) and neuropeptides (CGRP, NPFF, VIP, Sub P, NGF) were compared between groups. RESULTS: Symptomatic VDT users had more years of VDT use ( = 0.0002), reduced corneal sensitivity ( = 0.02), lower Schirmer I ( < 0.0001), lower blink rate ( < 0.0001), and more partial glands ( < 0.001) than asymptomatic users. The daily hours of VDT use (6.4 vs. 6.2), tear osmolarity, immature and mature dendritic cell densities, and IVCM parameters were similar across the two groups. A weak negative correlation of corneal sensitivity was noted with OSDI ( = 0.03) and blink rate ( = 0.037). Mature dendritic cell density had a positive correlation ( = 0.009) with corneal sensitivity. Symptomatic users showed reduced NGF and elevated MMP-9 and IL-1α compared to asymptomatic VDT users. CONCLUSION: Symptomatic VDT users have reduced mechanical corneal sensitivity without morphological changes in the sub-basal corneal nerve structure. Reduced NGF and elevated tear IL1a and MMP-9 in symptomatic VDT users indicate ocular surface inflammation in VDT-associated dry eye disease.
Lai C, Liu L, Zhu M
… +8 more, Deng X, Zhang N, Zhang Y, Huang J, Zhang P, Jiang B, Zeng W, Ke M
Curr Eye Res
· 2026 Jun · PMID 42317042
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PURPOSE: Glucocorticoid-induced glaucoma (GIG) involves trabecular meshwork (TM) fibrosis, including excess extracellular matrix (ECM) deposition and myofibroblast transdifferentiation, which impairs aqueous humor outflo...PURPOSE: Glucocorticoid-induced glaucoma (GIG) involves trabecular meshwork (TM) fibrosis, including excess extracellular matrix (ECM) deposition and myofibroblast transdifferentiation, which impairs aqueous humor outflow. Selective laser trabeculoplasty (SLT) is an established and effective treatment for lowering intraocular pressure, yet its underlying cellular and molecular mechanisms remain incompletely understood. We investigated whether SLT can normalize the fibrotic phenotype and restore TM cell function in a steroid-treated primary human cell model. METHODS: Primary human TM cells were exposed to 100 nM dexamethasone (DEX) for 3 or 7 days, then treated with or without SLT (1.0 mJ). ECM proteins (fibronectin, collagen IV) and myofibroblast markers (α-SMA, vimentin, FSP-1) were analyzed by Western blot and immunofluorescence. Migration (scratch, transwell), phagocytosis (fluorescent beads), and proliferation (EdU) were assessed. RESULTS: DEX induced a flattened, myofibroblast-like morphology, ECM accumulation, and elevated myofibroblast marker expression. SLT markedly reduced these changes, approaching control levels in some cases. DEX-enhanced migration was abolished by SLT in scratch (-110% at 3 d, -95% at 7 d; < 0.001) and transwell assays (-117% at 3 d, -73% at 7 d; < 0.0001). SLT partially rescued DEX-impaired phagocytosis (+68% at 3 d; < 0.01) and proliferation (+37% at 3 d; < 0.001), with reduced efficacy after prolonged exposure. CONCLUSIONS: SLT mitigates early glucocorticoid-induced TM fibrosis and restores key cellular functions, supporting its potential as a disease-modifying approach for GIG.
Asaoka R, Murata H, Hirasawa K
… +4 more, Shimada S, Fujino Y, Matsuno M, Shoji N
Curr Eye Res
· 2026 Jun · PMID 42274076
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PURPOSE: To investigate the association between reliability of visual field (VF) and the entropy of the Bayesian posterior distribution of the threshold. MATERIALS AND METHODS: Subjects were comprised of 122 eyes of 73 p...PURPOSE: To investigate the association between reliability of visual field (VF) and the entropy of the Bayesian posterior distribution of the threshold. MATERIALS AND METHODS: Subjects were comprised of 122 eyes of 73 patients with primary open-angle glaucoma. The VF was measured using the newly developed variational Bayes linear regression visual field (VBLR-VF) twice within 3 months. The likelihood of this final probability distribution of the thresholds in the measured VF was calculated (Entropy index). The mean absolute error (MAE) of the total deviation (TD) values of the test-retest VFs was measured, and its relationship to fixation losses (FLs), false positives (FPs), false negatives (FNs), and the Entropy index (average of the 2 VFs) was investigated. In addition, the association between the difference in the mean deviation (MD; between 2 VFs) and the difference in the Entropy index (between 2 VFs) was investigated. RESULTS: The Entropy index was significantly associated with FL, FP, and FN, as well as with the MAE ( < .001). Furthermore, the difference in the Entropy index was significantly negatively associated with the difference in MD ( < .001). CONCLUSION: The Entropy index was significantly associated with FL, FP, FN, and test-retest reproducibility. In addition, a higher Entropy index was associated with advanced VF loss, potentially indicating lower test reliability.
Chi J, Liu X, Song W
… +4 more, Chen W, Xue X, Zhang Y, Zhu W
Curr Eye Res
· 2026 Jun · PMID 42272331
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PURPOSE: Diabetic retinopathy (DR) is a leading cause of blindness, but its underlying molecular mechanisms remain poorly understood. This study aimed to investigate the role of STOM in DR-related retinal angiogenesis an...PURPOSE: Diabetic retinopathy (DR) is a leading cause of blindness, but its underlying molecular mechanisms remain poorly understood. This study aimed to investigate the role of STOM in DR-related retinal angiogenesis and to elucidate its potential signaling mechanism. METHODS: A streptozotocin-induced diabetic rat model and human retinal microvascular endothelial cells (HRMECs) exposed to high glucose were employed. The expression levels of STOM, vascular endothelial growth factor A (VEGFA), and extracellular signal-regulated kinase (ERK1/2) pathway-related molecules were detected by quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting (WB), and immunohistochemistry (IHC). Functional assays including Cell Counting Kit-8 (CCK-8), Direct cell counting, wound healing, Transwell migration, and Matrigel tube formation were performed to assess the effects of knockdown or overexpression on HRMECs. The ERK1/2 inhibitor U0126 was applied to verify pathway dependence. RESULTS: STOM expression was significantly upregulated in the retinas of diabetic rats and in HRMECs under high glucose conditions. silencing suppressed high glucose-induced proliferation, migration, and angiogenic tube formation in HRMECs. Whereas overexpression enhanced these pathological behaviors. Mechanistically, STOM promoted VEGFA upregulation and angiogenesis through activation of the ERK1/2 signaling pathway. CONCLUSIONS: STOM facilitates pathological retinal angiogenesis in diabetic retinopathy the ERK1/2/VEGFA signaling pathway. These findings identify STOM as a potential therapeutic target for DR.
Gopi S, Prethiba S, Chandhru M
… +9 more, Madesh S, Hariharan S, Palaniappan S, Rajagopal R, Alfarhan A, Almutairi BO, Choi KC, Kumaradoss KM, Arockiaraj J
Curr Eye Res
· 2026 Jun · PMID 42237548
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PURPOSE: The pathogenesis of diabetic retinopathy involves oxidative stress, inflammation, and neuronal dysfunction, with oxidative stress playing a critical role in retinal cell injury. The current study evaluates the t...PURPOSE: The pathogenesis of diabetic retinopathy involves oxidative stress, inflammation, and neuronal dysfunction, with oxidative stress playing a critical role in retinal cell injury. The current study evaluates the therapeutic potential of 3-(4-fluorophenyl)-4-(4-nitrophenyl)-1,2-oxazolidine, a fluorinated oxazolidine derivative with potent anti-inflammatory, antioxidant, and antidiabetic properties, in mitigating diabetic retinopathy-induced retinal damage using a zebrafish model. METHODS: Adult zebrafish were divided into five groups: control (group I, no intervention), STZ-induced diabetic retinopathy (group II, 50 μL of 7 mg/mL STZ administered intraperitoneally followed by 1% glucose exposure for 30 min, with an intravitreal injection of 20 μL of 7% STZ on day 7), 3-(4-fluorophenyl)-4-(4-nitrophenyl)-1,2-oxazolidine low dose (group III, 50 μM 3-(4-fluorophenyl)-4-(4-nitrophenyl)-1,2-oxazolidine administered intraperitoneally on days 14 and 21 post-induction), 3-(4-fluorophenyl)-4-(4-nitrophenyl)-1,2-oxazolidine mid dose (group IV, 100 μM 3-(4-fluorophenyl)-4-(4-nitrophenyl)-1,2-oxazolidine administered intraperitoneally on days 14 and 21 post-induction), and 3-(4-fluorophenyl)-4-(4-nitrophenyl)-1,2-oxazolidine high dose (group V, 200 μM 3-(4-fluorophenyl)-4-(4-nitrophenyl)-1,2-oxazolidine administered intraperitoneally on days 14 and 21 post-induction). Retinal histomorphometry, optomotor response, oxidative stress markers, and inflammatory markers were assessed across all groups. RESULTS: 3-(4-Fluorophenyl)-4-(4-nitrophenyl)-1,2-oxazolidine treatment at 200 μM concentration significantly reduced ROS accumulation, lipid peroxidation, and restored antioxidant enzyme levels, indicating its potent antioxidant activity. Histopathological analysis revealed a marked reduction in retinal neuronal degeneration, preserved retinal structure, and enhanced neuronal integrity. Behavioral analysis showed improved visual function, with 3-(4-fluorophenyl)-4-(4-nitrophenyl)-1,2-oxazolidine-treated zebrafish displaying improved optokinetic and optomotor response with improved swimming behavior, suggesting functional preservation of retinal activity. Furthermore, molecular analysis revealed the modulation of key oxidative stress markers and pro-inflammatory cytokines such as , with the suppression underscoring 3-(4-fluorophenyl)-4-(4-nitrophenyl)-1,2-oxazolidine's ability to mitigate inflammation and oxidative damage. CONCLUSION: These findings highlight the therapeutic efficacy of 3-(4-fluorophenyl)-4-(4-nitrophenyl)-1,2-oxazolidine in preventing diabetic retinopathy-related retinal degeneration by reducing oxidative stress and preserving retinal function, suggesting further investigation into its clinical applicability for managing retinal diseases linked to oxidative stress and inflammation.
Lu X, Wang M, Yan M
… +6 more, Liu H, Li X, Zheng X, Xu M, Li R, Hou L
Curr Eye Res
· 2026 Jun · PMID 42237526
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PURPOSE: To investigate the serum levels of ghrelin and Nod-like receptor protein 3 (NLRP3) in patients with diabetic retinopathy (DR) and evaluate their correlation with DR progression. METHODS: Thirty-seven patients wi...PURPOSE: To investigate the serum levels of ghrelin and Nod-like receptor protein 3 (NLRP3) in patients with diabetic retinopathy (DR) and evaluate their correlation with DR progression. METHODS: Thirty-seven patients with DR admitted to the First People's Hospital of Xianyang between April 2024 and April 2025 were enrolled and classified into non-proliferative DR (NPDR) and proliferative DR (PDR) subgroups based on fundus lesion severity. Fifty-three patients with simple cataracts served as controls. Serum levels of ghrelin and NLRP3 were measured using enzyme-linked immunosorbent assay, and their relationship with systemic indicators was analyzed. RESULTS: Serum ghrelin and NLRP3 levels differed significantly between the PDR, NPDR, and control groups ( < 0.001). Pairwise comparisons revealed statistically significant differences in serum ghrelin levels between the PDR and control groups, as well as between the NPDR and control groups (both < 0.017). Serum NLRP3 levels differed significantly between the PDR and control, the PDR and NPDR, and the NPDR and control groups (all < 0.017). Serum ghrelin levels were positively correlated with high-density lipoprotein levels ( = 0.325, < 0.05) and the use of statin lipid-lowering drugs ( = -0.397, < 0.05). CONCLUSIONS: Decreased serum ghrelin and elevated serum NLRP3 levels in patients with DR suggest that ghrelin and NLRP3 are involved in DR pathogenesis.
Karl NAM, Schuhmayer AC, Pomberger L
… +8 more, Eidherr M, Khalil H, Kallab M, Rothbächer J, Strohmaier C, Huemer J, Bolz M, Reisinger AS
Curr Eye Res
· 2026 Jun · PMID 42227873
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PURPOSE: Vascular endothelial growth factor (VEGF) is a factor in the pathogenesis of Age-Related Macular Degeneration (AMD) and Diabetic Macular Edema (DME), yet they differ in pathogenesis. It has been shown that only...PURPOSE: Vascular endothelial growth factor (VEGF) is a factor in the pathogenesis of Age-Related Macular Degeneration (AMD) and Diabetic Macular Edema (DME), yet they differ in pathogenesis. It has been shown that only patients with diabetic retinopathy have elevated VEGF levels in the aqueous humor. Intravitreal injections of anti-VEGF substances have been the gold standard in treating diseases for several years, but an impact on ocular perfusion has been assumed. This study aimed to investigate the effects of intravitreal aflibercept injection (IVI) on ocular perfusion in patients with AMD and DME. METHODS: This prospective study included 36 eyes of 36 patients, with 18 patients having nAMD ( = 18) and 18 patients having DME ( = 18), all treated with IVI. Ocular perfusion was measured using Laser Speckle Flowgraphy (LSFG). The parameter Mean Blur Rate (MBR) reflects erythrocyte flow velocity and serves as an indirect marker of perfusion. MBR was measured at the optic nerve head (ONH). The device's software can analyze MBR in areas of major retinal vessels (MV) and in microperfusion areas of the tissue (MT). Measurements were conducted at three time points (before scheduled IVI, as well as 1 week and 4 weeks after). RESULTS: In patients with AMD, significant decrease in MV was observed, while no significant change was noted for MV in patients with DME (Analysis of Variance, ANOVA, = 0.04 vs. = 0.2). However, both groups showed a significant decrease in MT (ANOVA, < 0.001 for both groups). CONCLUSION: The results indicate that retinal perfusion as measured with LSFG is less impaired in patients with DME following IVI treatment. This could be related to endothelial dysfunction, which appears to be restricted to retinal endothelial cells, as MT as a surrogate marker of choroidal perfusion showed a significant reduction in the DME group. Responses highlight physiological differences between retinal and choroidal capillaries.
Curr Eye Res
· 2026 May · PMID 42206905
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PURPOSE: Epidemiological studies yielded conflicting results regarding the relationship between cardiometabolic factors and age-related macular degeneration (AMD). However, the methodological characteristics of these stu...PURPOSE: Epidemiological studies yielded conflicting results regarding the relationship between cardiometabolic factors and age-related macular degeneration (AMD). However, the methodological characteristics of these studies, which may partly explain this controversy, are not currently addressed. This narrative review aimed to examine current evidence between the six most studied cardiometabolic factors and AMD, focusing on identifying key methodological shortcomings and discussing analytical approaches currently available to address them. METHODS: We conducted a rigorous, nonsystematic literature search using targeted MeSH terms and keywords in MEDLINE (PubMed), EMBASE, Web of Science and Scopus, with no language restrictions, up to June 2025. We identified and reviewed epidemiological (cross-sectional, case-control, cohort) studies reporting original data on the six targeted cardiometabolic factors: blood pressure, antihypertensive medications, lipid levels, lipid-lowering medications, diabetes mellitus and antidiabetic treatments. A quantitative synthesis of studies was conducted to describe their methodological characteristics and reported associations. RESULTS: Across the 116 reviewed associations, prospective cohorts (41%) and cross-sectional designs (37%) predominated. Most originated from America (35%) and Europe (32%). Lipids (21%) and lipid-lowering agents (20%) were the most frequently studied exposures, while advanced AMD was the predominant outcome (56%). Logistic regression was the main analytic approach (70%), and association conclusions were most often null (42%), followed by increased (36%) and decreased (22%) risk. The most common methodological limitations included cross-sectional study designs, static modeling of dynamic exposures, unaddressed interval censoring, not controlling for confounding by indication, and unstandardized selection of confounders, which are likely to bias the reported associations. CONCLUSIONS: Future studies should prioritize robust methodological frameworks, including longitudinal designs, survival bias mitigation, standardized and repeated exposure assessments, distinction between AMD subtypes, propensity scores for medications use, and advanced causal inference techniques wherever feasible. Such an effort is foundational to strengthening the validity and reproducibility of findings linking cardiometabolic factors to AMD, thereby improving AMD prevention strategies.
Curr Eye Res
· 2026 May · PMID 42206882
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PURPOSE: To evaluate TeaRx, a 10-minute, multi-parametric tear test, as a single point-of-care diagnostic device for assessment of dry eye disease (DED), stratifying severity, identifying severe meibomian gland dysfuncti...PURPOSE: To evaluate TeaRx, a 10-minute, multi-parametric tear test, as a single point-of-care diagnostic device for assessment of dry eye disease (DED), stratifying severity, identifying severe meibomian gland dysfunction (MGD), and predicting patient response to topical cyclosporine A (CysA) therapy. METHODS: A single center, observational, longitudinal clinical study enrolled 593 participants graded by TFOS DEWS II criteria: 495 DED (including 83 with severe MGD), and 98 healthy controls. Tear fluid was collected using a microfluidic tear collection device and analyzed for five biomarkers (lactoferrin, human serum albumin, lysozyme, mucin and IgA) by lateral-flow immunochromatographic assay (LFIA). Optimal logistic regression models were selected for differentiating DED vs. healthy, severe vs. non-severe DED, severe MGD vs. non-MGD in DED patients, and prediction (at baseline) of CysA responsiveness. RESULTS: Based on the models selected, TeaRx differentiated DED (at all severity levels) from healthy controls with 71.5% sensitivity, 63.1% specificity, and AUC = 0.72. Severe DED was differentiated from non-severe DED with 80.6% sensitivity, 66.7% specificity, AUC = 0.77. Severe MGD within DED was identified with 80.6% sensitivity, 61.3% specificity, AUC = 0.80. TeaRx predicted CysA responsiveness with 93.8% sensitivity, 63.1% specificity, AUC = 0.86, and NPV = 92.3%. CONCLUSIONS: Based on the results of the current study, TeaRx may potentially offer the means for rapid, noninvasive tear biomarker profiling within 10 minutes, providing accurate diagnosis of DED, severity stratification, detection of severe MGD, and prediction of therapeutic response to CysA. These results support its role as a personalized diagnostic platform for optimizing management of DED.
Curr Eye Res
· 2026 May · PMID 42189959
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PURPOSE: Calcium signaling is closely linked to smooth muscle contraction. The ciliary muscle, an intraocular smooth muscle essential for eye focusing, undergoes spasm as the main cause of accommodation spasm. This study...PURPOSE: Calcium signaling is closely linked to smooth muscle contraction. The ciliary muscle, an intraocular smooth muscle essential for eye focusing, undergoes spasm as the main cause of accommodation spasm. This study aimed to investigate the role of ciliary muscle calcium signaling in this condition. METHODS: An accommodation spasm model was established in guinea pigs using carbachol eye drops. Measurements were taken at 7, 14, 21, and 28 days post-administration, including refractive status (retinoscopy), ciliary muscle morphology (light microscopy), calcium concentration (microplate assay), IP3 level (ELISA), and IPR/RYR expression (qRT-PCR and western blotting). RESULTS: In the model eyes, carbachol treatment for 7, 14, 21, and 28 days induced significant myopic refraction, manifesting as accommodation spasm. The ciliary muscle fibers were more densely packed in the model group than in the normal group. Moreover, calcium and IP concentrations were higher in the model group in a treatment duration‑dependent manner, peaking at 28 days. The ratio of IPR and RYR protein expression increased in the model group compared to the normal group and was dependent on the duration of medication; IPR expression was the highest after 28 days, and RYR expression was the highest after 21 days. The ratio of IPR and RYR mRNA expression increased in the model group compared to the normal group; IPR expression was higher on the 7, 21, and 28 days, and RYR expression was higher on the 28 day. CONCLUSIONS: The continuous carbachol-induced contraction of the ciliary muscle led to an increase in the concentration of Ca in the tissue. Meanwhile, the activation of the intracellular calcium reservoir membrane proteins IPR and RYR further led to the release of Ca. These findings indicate that calcium signaling of the ciliary muscle may contribute to accommodation spasms.
Curr Eye Res
· 2026 May · PMID 42179133
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PURPOSE: This study aimed to elucidate the effects and mechanisms of microRNA-146a on the proliferation, apoptosis, migration, and epithelial-mesenchymal transition (EMT) of human lens epithelial cells (HLECs). METHODS:...PURPOSE: This study aimed to elucidate the effects and mechanisms of microRNA-146a on the proliferation, apoptosis, migration, and epithelial-mesenchymal transition (EMT) of human lens epithelial cells (HLECs). METHODS: Anterior capsular tissue obtained during surgery from the age-related cataract (ARC) group and the control group was collected; the tissue was ground and subjected to RT-qPCR experiments to analyze the expression of microRNA-146a; in experiments, TNF-α (20 ng/ml) induced human lens epithelial cells (HLECs) to establish an inflammatory injury cell model; Transfection of TNF-α-treated HLECs with microRNA-146a mimics and STAT1 overexpression plasmid; RT-qPCR, Western The blotting method was used to detect the mRNA and protein expression levels of EMT markers (E-cadherin, Vimentin, a-SMA) after cell treatment; the transwell assay and cell scratch experiment were used to detect changes in the migration ability of cells after treatment; the CCK8 assay was used to detect cell proliferation after treatment Changes in ability; flow cytometry was used to detect changes in cell apoptosis before and after cell treatment. RT-qPCR and Western blotting were used to detect the STAT1/MYC pathway mRNA and protein expression levels after cell treatment. RESULTS: The expression of microRNA-146a in the capsules of patients with age-related cataracts was lower than that in the control group, and the mRNA expression of TNF-α was significantly higher than that in the control group. Induction by TNF-α (20 ng/ml) can cause inflammatory damage to normal HLECs and significantly change the expression of microRNA-146a and EMT-related genes in HLECs. Overexpression of microRNA-146a reverses TNF-α-induced EMT in HLECs. microRNA-146a affects the STAT1/MYC pathway by targeting and regulating STAT1. CONCLUSION: MicroRNA-146a directly targets STAT1 and inhibits TNF-α-induced proliferation, migration, and EMT of lens epithelial cells through the STAT1/MYC pathway, exerting a protective effect.
Gijs M, Enríquez-de-Salamanca A, Hagan S
… +2 more, Grzybowski A, Versura P
Curr Eye Res
· 2026 May · PMID 42141967
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PURPOSE: Tear fluid biomarker research is rapidly growing in both ocular and non-ocular diseases, with biomarker-based tests gradually transitioning into clinical applications. As this progress continues, translation int...PURPOSE: Tear fluid biomarker research is rapidly growing in both ocular and non-ocular diseases, with biomarker-based tests gradually transitioning into clinical applications. As this progress continues, translation into routine practice remains limited. This perspective aims to summarize key advances with direct clinical relevance and identify the major barriers that must be overcome for widespread adoption. METHODS: This perspective is based on the authors' multidisciplinary expertise combined with a focused review of the current literature on tear fluid biomarkers and point-of-care applications. RESULTS: Several substances identified in tear fluid have been considered as potential biomarkers. As a result, specific point-of-care tests have reached the market, with several more close to clinical development. While these tests offer objective and quantifiable values, significant challenges persist, including suboptimal sensitivity and specificity, lack of standardized collection and analysis protocols, absence of validated reference ranges and diagnostic thresholds, regulatory and reimbursement barriers, and limited clinical awareness. Importantly, most current applications remain focused on diagnosis, while unmet clinical needs such as prognostication, therapy guidance, and longitudinal monitoring remain underexplored. CONCLUSION: To achieve meaningful clinical integration, research must progress from discovery to standardization, validation, and alignment with real-world needs. Addressing these challenges is essential to incorporate the analysis of tear fluid biomarkers into routine care and advance precision diagnostics and personalized therapy in ophthalmology and related fields.
Curr Eye Res
· 2026 May · PMID 42132222
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PURPOSE: Human retinal microvascular endothelial cell (HRMEC) dysfunction contributes to retinal vascular diseases. This study aimed to elucidate the molecular role of TIE2 in HRMEC angiogenesis and identify its intracel...PURPOSE: Human retinal microvascular endothelial cell (HRMEC) dysfunction contributes to retinal vascular diseases. This study aimed to elucidate the molecular role of TIE2 in HRMEC angiogenesis and identify its intracellular regulatory mechanisms. METHODS: TIE2 knockdown HRMECs were established using lentiviral shRNA. Proliferation was assessed by CCK-8 assay, angiogenesis by Matrigel tube formation, apoptosis by flow cytometry, and transcriptome by RNA sequencing. TIE2-major vault protein (MVP) interaction was validated by co-immunoprecipitation and immunofluorescence. PI3K/AKT pathway involvement was examined using a specific inhibitor. RESULTS: TIE2 knockdown significantly suppressed HRMEC proliferation (A450 nm; 24h: 0.97 ± 0.04, 0.98 ± 0.03, 0.86 ± 0.03, > 0.05; 48h: 1.87 ± 0.16, 1.86 ± 0.04, 1.57 ± 0.02, < 0.0001; 72h: 2.14 ± 0.05, 2.15 ± 0.04, 1.90 ± 0.04, < 0.001) and tube formation (total number of tubes: 10.00 ± 1.00, 9.67 ± 0.58, 6.33 ± 0.58, < 0.01) while promoting apoptosis (%: 3.55 ± 0.16, 3.96 ± 0.37, 7.25 ± 1.13, < 0.01). Transcriptomic analysis revealed extensive gene expression changes associated with knockdown, with enrichment in pathways related to ion channel activity, neuroactive ligand-receptor interaction, and calcium signaling. Co-immunoprecipitation identified MVP as a TIE2-interacting protein, while immunofluorescence provided supportive evidence for a partially overlapping distribution of detectable TIE2 and MVP signals in control HRMECs. Functionally, MVP knockdown attenuated agonist-induced angiogenesis (total number of tubes: 22.67 ± 1.16 vs. 18.33 ± 0.58, < 0.0001), whereas MVP overexpression partially rescued angiogenic defects caused by TIE2 knockdown (9.00 ± 1.00 vs. 20.33 ± 2.08, < 0.0001). These effects were dependent on activation of the PI3K/AKT signaling pathway (total number of tubes: 28.33 ± 0.58 vs. 23.33 ± 1.53, < 0.0001). CONCLUSIONS: TIE2 is an important regulator of HRMEC angiogenic function. Our findings suggest that TIE2 interacts with MVP and modulates angiogenic responses, at least in part through PI3K/AKT signaling. These results provide mechanistic insight into retinal endothelial biology and identify the TIE2-MVP axis as a potential therapeutic target in retinal vascular diseases.
PURPOSE: Trabecular meshwork (TM) cells play a role in the regulation of aqueous humor outflow. In glaucoma, a large number of TM cells exhibiting mesenchymal phenotypes is associated with abnormal turnover of extracellu...PURPOSE: Trabecular meshwork (TM) cells play a role in the regulation of aqueous humor outflow. In glaucoma, a large number of TM cells exhibiting mesenchymal phenotypes is associated with abnormal turnover of extracellular matrix components including collagen, leading to high intraocular pressure (IOP). Integrin α2 is a collagen receptor, although its role in TM cells is unknown. In this study, we assessed the role of integrin α2 in TM cells. METHODS: We assessed the expression of integrin α2 and cell phenotypes in human TM cells using western blot analysis, immunohistochemistry and collagen contraction assays. The integrin α2 inhibitor BTT3033 and an integrin α2-targeting small interfering RNA (siRNA) were used to assess the roles of integrin α2 in TM cells. RESULTS: Transforming growth factor (TGF)-β2 stimulation decreased integrin α2 expression, and transfection of cells with integrin α2 siRNA enhanced mesenchymal phenotypes. In contrast, cells treated with the integrin α2 inhibitor BTT3033 tended to exhibit more endothelial features than mesenchymal features, and BTT3033 increased integrin α2 expression due to the accumulation of integrin α2 at the plasma membrane. BTT3033 also attenuated mesenchymal characteristics, along with decreasing Smad2 phosphorylation and reducing collagen contraction. The induction of endothelial characteristics by BTT3033 was observed even in the presence of TGF-β2. CONCLUSION: The expression level of integrin α2 is a determinant of endothelial characteristics in TM cells, and pharmacological modulation of integrin α2 by BTT3033 promotes an endothelial phenotype, thus offering a novel therapeutic strategy for IOP regulation.