Current Eye Research最新文献

Purpose: The purpose of this study was to investigate the role and mechanism of caspase-8 in the development of choroidal neovascularization induced by age-related macular degeneration, with the aim of identifying a potential therapeutic target for neovascular age-related macular degeneration.

Methods: Mouse models of laser photocoagulation-induced choroidal neovascularization and hypoxic human choroidal endothelial cells were utilized to examine the involvement of caspase-8 in choroidal neovascularization development. The toll-like receptor 4/TIR domain-containing adaptor molecule 1/caspase-8 pathway was explored in hypoxic human choroidal endothelial cells to elucidate its contribution to pathological angiogenesis. Various experimental techniques, including inhibition assays and immunoblotting analysis, were employed to assess the effects and mechanisms of caspase-8 activation.

Results: Inhibition of caspase-8 demonstrated attenuated choroidal neovascularization development in mice subjected to laser photocoagulation. Activation of the toll-like receptor 4/TIR domain-containing adaptor molecule 1/caspase-8 pathway was observed in hypoxic human choroidal endothelial cells. Upon activation by the toll-like receptor 4/TIR domain-containing adaptor molecule 1 axis, caspase-8 directly cleaved caspase-1, leading to the cleavage of interleukin-1β and interleukin-18 by caspase-1. Consequently, activation of interleukin-1β and interleukin-18 through the toll-like receptor 4/TIR domain-containing adaptor molecule 1/caspase-8/caspase-1 pathway promoted the proliferative, migratory, and tube-forming abilities of hypoxic human choroidal endothelial cells.

Conclusion: The findings of this study indicate that caspase-8 plays a crucial role in promoting choroidal neovascularization by activating interleukin-1β and interleukin-18 through the toll-like receptor 4/TIR domain-containing adaptor molecule 1/caspase-8/caspase-1 pathway in choroidal endothelial cells. Therefore, targeting caspase-8 may hold promise as a therapeutic approach for neovascular age-related macular degeneration.

Purpose: The protein concentrations of apoptosis inducing factor (AIF), macrophage migration inhibitory factor (MIF), interleukin-1β (IL-1β), poly ADP ribose polymerase-1 (PARP-1), poly (ADP-ribose) (PAR), α-synuclein (α-SYN), monocyte chemotactic protein‑1 (MCP-1) and tumor necrosis factor-α (TNF-α) in the vitreous of eyes with rhegmatogenous retinal detachment associated with choroidal detachment (RRDCD) were observed and analyzed.

Methods: A total of 57 patients' samples were included. 30 patients with RRD were set as the control group, 27 patients with RRDCD were set as the experimental group (16 patients with preoperative glucocorticosteroid (GC+) and 11 patients without preoperative glucocorticosteroid (GC-)). The levels of AIF, MIF, IL-1β, PARP-1, PAR, α-SYN, MCP-1 and TNF-α in vitreous of patients in the control and experimental groups were detected by enzyme-linked immunosorbent assay (ELISA).

Results: The concentration of AIF in the vitreous was higher in the RRD group (9.96 ± 2.78 ng/ml) than in the RRDCD (GC+) group (7.65 ± 2.13 ng/ml, p = 0.006),the RRDCD (GC+) group was lower than the RRDCD (GC-) group (10.28 ± 2.81 ng/ml) (p = 0.013). The concentration of MIF in vitreous fluid was lower in the RRDCD (GC+) group (61.21 ± 17.56 ng/ml) than in the RRDCD (GC-) group (74.30 ± 9.66 ng/ml, p = 0.039). In the experimental group, the protein concentration of MCP-1 in the RRDCD (GC+) group was higher in the preoperative PVR grading C (284.93 ± 54.96 ng/ml) grade than in the D grade (225.94 ± 24.05 ng/ml) (p = 0.050); The protein concentration of MIF was lower in the RRDCD (GC+) group of patients with an ocular axis of <26 mm (56.19 ± 6.99 ng/ml) than in those with an ocular axis of ≥26 mm (76.26 ± 26.60 ng/ml, p = 0.043).

Conclusion: Low expression of Parthanatos-related proteins is present in the vitreous of patients with RRDCD (GC+), and preoperative treatment with glucocorticoids may reduce the expression of Parthanatos-related proteins.

Purpose: To extend cross-sectional data on cytokine ratios (CRs) in dry eye disease (DED) signs by investigating longitudinal change in pro- to anti-inflammatory CRs and associations with change in DED signs and symptoms.

Methods: Secondary analysis of fifty-four subjects [mean age 57.3 (SD 13.2) years, 85.2% female; 68.5% white] with ≥ 4 uL pooled tear volumes at months 0, 6, and 12. Pro-inflammatory (IL-1b, IL-6, IL-8, IL-17A, IFN-g, and TNF-a) to anti-inflammatory (IL-6, IL-10) cytokine ratios (CR) were calculated. DED signs (corneal and conjunctival staining scores, tear break-up time, Schirmer test, Meibomian gland plugging, tear osmolarity, composite sign severity score) and symptoms [Ocular Surface Disease Index (OSDI)] were measured. Changes over time in DED signs, symptoms, and CRs were evaluated using longitudinal models. Correlations between changes in CR and changes in DED signs and symptoms were evaluated using Spearman correlation coefficients (rho).

Results: DED signs which improved over time (p < 0.001) included corneal and conjunctival staining score, tear break-up time, tear osmolarity, and composite sign severity score. Using IL-10 as anti-inflammatory, changes in corneal and conjunctival staining and composite severity score significantly correlated with changes in pro- to anti-inflammatory CRs from month 0 to 6 (|rho|: 0.29-0.45, p: 0.003-0.04) but not between month 0 to 12 (|rho|: 0.01 to 0.24, all p > 0.08). DED symptoms decreased across one year (p < = 0.001) for all OSDI measures; these changes did not correlate with changes in CRs (|rho|: 0.00 to 0.29, all p > 0.04).

Conclusions: Improvement in some DED signs across one year correlated weakly with decreases in pro- to anti-inflammatory CRs, in alignment with the understanding of DED as inflammatory. CRs may provide greater insight than absolute tear cytokine concentrations as possible DED biomarkers. Additional studies that provide standardized clinical information and tear collection and analysis are needed to validate CRs in DED.

Purpose: Myopia is a complex disorder with etiology involving an interplay between several genetic and environmental factors. Interphotoreceptor retinoid-binding protein (IRBP) is found in the subretinal space and is crucial in the visual cycle. The interphotoreceptor retinoid-binding protein knockout mouse (IRBP KO) was established as a model system to understand myopia and retinal degeneration. The current study investigated genes associated with myopia, retinal homeostasis, and inflammation in IRBP KO.

Methods: RNA from retinas of congenic IRBP KO and wild-type C57BL/6J (WT) mice at postnatal day 5 (P5), P40, and P213 were subjected to digital droplet PCR (ddPCR) using a Bio-Rad automated droplet generator and QX200 reader. Target genes were selected based on genome-wide association studies, animal models, myopia studies, and other genes associated with retinal homeostasis and inflammation. HPRT, a housekeeping gene, was used for normalization. An average expression ratio (target/HPRT) and standard deviation (SD) were calculated. ANOVA assessed statistical significance, and a p < 0.05 was considered significant.

Results: The ddPCR data analysis indicated that numerous myopia and inflammation-associated genes were differentially regulated in IRBP KO retinas with distinct temporal variation (upregulated at P5, decreased at P40, and no change at P213 relative to WT). C1qa, Gjd2, Sntb1, and Vsx2 emerged as top genetic candidate pathways. Compared with WT, immunoblotting analysis of C1qa showed no significant differences at P5 but significantly increased protein levels at P7 in IRBP KOs. Vsx2 remained unaltered at P5 and P7 in KO when compared with WT.

Conclusions: Data analysis indicated significant contributions from C1q, Gjd2, Sntb1, and Vsx2 genes in IRBP deficiency.

Purpose: Central retinal artery occlusion, also known as an eye stroke, results in visual impairment and functional challenges. Our study objectives were to identify meaningful measures and factors that indicate or enable successful recovery after eye stroke and to determine optimal processes to support research, including exploring barriers and facilitators to successful research participation.

Methods: We used qualitative methods including the 5Ts Framework (target population identification, team composition, time considerations, tips to accommodate older adults, tools for inclusive enrollment of older adults) to provide a guide to the development of the semi-structured interviews and to help facilitate the research process such as the set-up of interviews. We enrolled three groups: individuals living with the sequelae of eye stroke, care partners, and health care providers. We conducted a descriptive content analysis with an inductive approach.

Results: Twenty-five people participated. This group included 10 eye stroke survivors (median age, 62.5; range, 56-84 years; 20% were women), 4 care partners (median age, 57 years; range, 56-59 years; 100% were women), and 11 health care providers (median age, 33 years; 25-60 years; 54.5% were women). Four themes emerged from the data: (1) returning to full independence, (2) family support, (3) strategies for participation, and (4) lack of accessibility.

Conclusions: The themes identified by participant groups indicated that strategies such as providing sufficient lighting and incorporating family support are key for research participation by individuals with vision impairment related to eye stroke. Furthermore, it is essential that researchers determine ways to address inequities, including lack of accessibility to research sites. This work has implications for how research teams develop research processes and implement research findings into clinical settings for eye stroke survivors.

Purpose: To retrospectively describe the performance of topical insulin in persistent corneal epithelial defects (CED) and persistent corneal ulcers.

Methods: We reviewed cases of patients treated for persistent CED and persistent corneal ulcers using topical insulin in a concentration of 25 IU per milliliter three times per day. The closure rate of CED and corneal ulcers was the main outcome measure.

Results: Thirty-seven episodes of 29 patients treated with topical insulin were reviewed. There was a wide range of additionally used medication, underlying pathologies as well as ocular and systemic comorbidities in our cohort. On average, insulin drops were started after 36 days of conventional therapy (SD 59, range 0-193) and were used for 42 days (SD 38, range 3-130). Therapy success was achieved in 15 of 28 (53.5%) cases with CED and in 4 of 9 (44%) cases with corneal ulcers. While insulin generally showed a good safety profile, one patient reported intolerable discomfort related to the use of topical insulin.

Conclusion: Topical insulin may be considered as a treatment option in complicated cases refractory to conventional treatment, but outcomes may be less favorable than previously reported.

Purpose: This study aims to conduct a mini review of published literature concerning the role of exosomes in the field of ophthalmology, with a specific focus on Age-Related Macular Degeneration (AMD).

Methods: In this study, a comprehensive search was conducted using PubMed and Google Scholar to identify relevant publications. Additionally, trials submitted to clinicaltrials.gov were reviewed to identify further relevant articles. The selected studies specifically focused on the ocular implications of exosomes in Age-Related Macular Degeneration.

Results: Exosomes, small extracellular vesicles measuring less than 200 nm, play a crucial role in cell signaling and are involved in various physiological and pathological processes. Recent research has focused on utilizing exosomes for disease detection and treatment. Studies have investigated the ocular implications of exosomes, particularly in AMD. Exosomes found in aqueous fluid and blood have been examined as potential markers for AMD and as indicators of treatment response. Additionally, research in animal models has indicated the potential of exosomes in preventing AMD, as well as their promise for targeted and efficient drug delivery. This mini review primarily emphasizes the clinical aspects of publications related to AMD, rather than focusing solely on basic science.

Conclusions: Exosomes have a great potential for understanding Age-related Macular Degeneration and effective and targeted treatment for retinal diseases.

Purpose: This study aimed to initially test whether machine learning approaches could categorically predict two simple biological features, mouse age and mouse species, using the retinal segmentation metrics.

Methods: The retinal layer thickness data obtained from C57BL/6 and DBA/2J mice were processed for machine learning after segmenting mouse retinal SD-OCT scans. Twenty-two models were trained to predict the mouse groups. The best neural network model was optimized for better outcomes. Prediction accuracy, the area under the curve, sensitivity, specificity, precision, and F-1 score values were obtained.

Results: The Wilcoxon Signed-Rank test provided significantly higher validation accuracy for neural networks than decision trees, discriminant analysis, support vector machines, and k-nearest neighbor classifiers (p = 0.005 for all). For C57BL/6-DBA/2J classification, a mean validation accuracy of 88.11 ± 3.92% (95% CI: 86.99-89.22) was achieved for the neural network when the optimized neural network had 92.31% final test accuracy with an area under the curve value of 0.9762, 94.44% sensitivity, 90.48% specificity, 89.47% precision, and 0.92 F-1 score. The optimized neural network model for age group differentiation had a final test accuracy of 82.05% with a 0.9064 area under the curve value, 77.27% sensitivity, 88.24% specificity, 89.47% precision, and 0.83 F-1 score.

Conclusions: These findings validate that machine learning, using segmentation metrics instead of images, can effectively analyze retinal OCT scans in mice for categorical predictions in experimental models. Expanding this approach with additional features, including histopathological and functional correlations, is expected to improve the prediction power further, promising valuable applications to predict more complex outcomes in experimental and clinical studies.

Purpose: to investigate the association between vascular endothelial growth factor (VEGF)-2578C/A polymorphism and susceptibility to type 2 diabetic retinopathy (T2DR) by meta-analysis.

Methods: According to the search strategy, Four databases were retrieved to identify the literature on the relationship between VEGF polymorphism and the risk of T2DR from inception to July 2024. Stata 15.0 was used for data processing.

Results: Ten articles were involved in this review, covering 1390 cases and 1306 controls. The pooled results exhibited that the risk of T2DR was associated with VEGF-2578C/A polymorphism under the allele model (A/C: OR= 1.33, 95%CI: 1.04-1.72, p = 0.025) and dominant models (AA+CA/CC: OR= 1.38, 95%CI: 1.00-1.91, p = 0.047). However, in recessive, homozygous, and heterozygous models, no significant difference was observed (all p > 0.05).

Conclusions: The VEGF-2578C/A polymorphism is associated with susceptibility to T2DR. In particular, allele A and genotype AA+CA at the VEGF-2578C/A locus were significantly associated with an increased risk of T2DR.