Current Eye Research最新文献

Purpose: This study explored the regulatory role of microglia in retinal vascular development, particularly their effects on vascular bifurcation and maturation. The study aimed to elucidate how microglia influence retinal vascular complexity and maturation.

Methods: Using CX3CR1^GFP/+ reporter and pharmacological depletion mouse model, retinas were analyzed at P42 via immunofluorescence staining and confocal microscopy. Primary brain-derived microglia and brain microvascular endothelial cells were used for in vitro co-culture experiments. Quantitative assessments of vascular bifurcation points were performed via ImageJ software. Tangential frozen sections were used to analyze spatial relationships.

Results: The results revealed an increase in vascular bifurcation complexity, which was correlated with microglia density. Conversely, microglial depletion led to a significant reduction in vascular bifurcation, particularly in the peripheral retina, impairing the formation of the vascular network. In vitro, co-culture with microglia enhanced endothelial cell tube formation and sprouting.

Conclusion: Our findings reveal a strong association between microglial distribution and vascular patterning, supporting the role of microglia in normal retinal vascular development and offering perspectives for future research.

Purpose: This study aimed to uncover the mechanism of IGF2BP3/GSDMD axis by modulating JNK signaling activation in eyelid basal cell carcinoma (BCC).

Methods: Human BCC cell line (TE354.T) was transfected vectors targeting IGF2BP3 and GSDMD. Following transfection, changes in cell proliferation, migration, invasion, pyroptosis, and inflammatory response were monitored. Protein expression analysis was done with specific antibodies (IGF2BP3, GSDMD, GSMDM-N, p20, IL-1β, IL-18, JNK, p-JNK, and p-c-JUN). IGF2BP3 and GSDMD co-localization in TE354.T cells were observed. The m6A modification of GSDMD mRNA was detected by gene-specific m6A qPCR assay. Tumor growth was observed in nude mice.

Results: By stabilizing GSDMD mRNA, IGF2BP3 reduced eyelid BCC proliferation, invasion, and migration, and increased pyroptosis. IGF2BP3 regulated the expression and translational output of GSDMD in TE354.T cells. IGF2BP3/GSDMD axis acted in BCC by blocking JNK pathway activation. IGF2BP3 inhibited tumor formation by promoting GSDMD stability.

Conclusions: IGF2BP3 enhances GSDMD stability and blocks JNK signaling activation to promote eyelid BCC pyroptosis in an m6A-Dependent Manner.

Purpose: After Descemet Membrane Endothelial Keratoplasty (DMEK), the air-gas compound in the anterior chamber can lead to a postoperative increase in intraocular pressure (IOP) up to pupillary block. YAG laser iridotomy (IO) or surgical iridectomy (IE) is performed to prevent these painful and sight-threatening elevations. We aimed to compare the safety profiles of the two procedures.

Methods: We included a total of n = 196 eyes of N = 178 patients (55.6% female and 44.4% male) who underwent DMEK. Of these, 124 eyes received intraoperatively an IE (63.3%, group IE) and 72 an IO one day before the surgery (36.7%, group IO). A procedural imbalance between both groups has to be noted, as phakic patients often underwent IO and the pseudophakic ones always underwent IE. The primary endpoint was the incidence of elevated IOP. Secondary endpoints were the clinical outcome (measured by endothelial cell count (ECC), visual acuity (VA), central corneal thickness (CCT)) and risk factors for pressure elevation.

Results: Group IO showed a significantly higher incidence of postoperative IOP values above 50 mmHg (p = .021), a higher absolute IOP immediately after surgery compared to group IE (p = .004; ω² = .04) and a greater immediate IOP difference from preoperative to postoperative (p = .011, ω² = .03). This difference resolved after 6 weeks and VA did not differ significantly between the groups. In pseudophakic eyes, a deeper anterior chamber depth (ACD) was associated with smaller immediate IOP difference (p = .026; ω² = .06).

Conclusions: This study showed that preoperative laser IO might be an alternative to surgical IE, but sufficient postoperative pressure control and appropriate preoperative counseling are crucial as laser iridotomy is associated with a higher risk of peak pressure values > 50 mmHg and immediate pressure differences.

Purpose: Achromatopsia (ACHM) is a rare hereditary retinal disorder characterized by low vision, photophobia, and nystagmus. Due to its rarity, the relevant literature is limited. This study aimed to evaluate the structural and functional retinal changes observed in the ACHM spectrum using multimodal imaging.

Methods: In this prospective cross-sectional study, 62 eyes of 31 patients within the ACHM spectrum who applied to the Low Vision Rehabilitation Unit of Ankara University Faculty of Medicine were evaluated. Assessments included macular pigment optical density (MPOD), microperimetry, contrast sensitivity (CS), fundus autofluorescence (FAF), and optical coherence tomography (OCT). Eyes were classified into five stages based on photoreceptor layer damage.

Results: The mean best-corrected visual acuity (BCVA) was 0.85 ± 0.18 logMAR. Fundus examination showed normal findings in 42%, irregular retinal pigment epithelium (RPE) in 48%, and atrophic RPE in 10%. Mean MPOD was 1.32 ± 2.27 dB, retinal sensitivity 20.85 ± 4.61 dB, and central macular thickness (CMT) 124.88 ± 59.15 µm. Fixation was extrafoveal in 92% and unstable in 83%. Photoreceptor damage was present in 72% of eyes: stage 1 (28%), stage 2 (13%), stage 3 (14%), stage 4 (19%), and stage 5 (26%). The ellipsoid zone was absent in 59%, foveal hypoplasia in 52%, and hypoautofluorescence in 57%. Significant correlations were observed between ellipsoid zone integrity and age, CMT, and FAF pattern (p = 0.044, p = 0.005, p < 0.001).

Conclusion: This study highlights reduced MPOD, photoreceptor damage (72%), ellipsoid zone loss (59%), and foveal hypoplasia (52%) within the ACHM spectrum. The findings of this study may contribute to the literature on structural and functional retinal changes observed in cases within the ACHM spectrum and may be useful in the design of future clinical studies.

Purpose: Laser photocoagulation is widely used to treat peripheral retinal pathologies. This study aims to investigate its impact on the macula and identify associated risk factors.

Methods: This prospective observational study enrolled patients undergoing laser photocoagulation for peripheral retinal degeneration and/or breaks were enrolled. Ocular examinations, including optical coherence tomography (OCT), OCT angiography (OCTA), and multifocal electroretinography (mf-ERG), were conducted at baseline and at 1- and 3-month post-treatment. Data were analyzed using paired t-tests and Pearson's correlation.

Results: Thirty-four eyes from 34 patients were included. The foveal avascular zone area significantly enlarged (Δ = 0.21 ± 0.35mm², p = 0.038), and mf-ERG implicit times in perifoveal regions were prolonged (R3: Δ = 0.45 ± 0.70 ms, p = 0.027; R5: Δ = 0.85 ± 0.72 ms, p < 0.001) at 1 month following laser photocoagulation, with both parameters returning to baseline by 3 months. Laser photocoagulation also increased thickness in the parafoveal retinal nerve fiber layer (Δ = 1.72 ± 3.33 μm, p = 0.049), inner nuclear layer (Δ = 0.90 ± 1.35 μm, p = 0.014), and full-thickness foveal retina (Δ = 11.2 ± 21.1 μm, p = 0.043), with changes persisting up to 3 months (Δ = 2.74 ± 2.52 μm, p = 0.011; Δ = 0.79 ± 0.79 μm, p = 0.017; Δ = 8.51 ± 8.19 μm, p = 0.014, respectively). Correlation analysis revealed that both the number of laser spots and total laser energy were positively correlated with macular thickness, while the minimum distance between the laser and the fovea was negatively correlated with macular changes.

Conclusions: Peripheral retinal laser photocoagulation can induce foveal hypoperfusion, macular thickening, and prolonged implicit times. Although most of these changes are generally mild and reversible, macular thickening persisted throughout the 3-month follow-up period. Laser parameters, including the number of spots, energy, and distance from the fovea, are associated with macular changes.

Purpose: This study aimed to provide direct evidence of the potential role of N6-methyladenosine (m⁶A) modification in the progression of myopia. We focused on identifying genes that may be involved in scleral remodeling through m⁶A regulation in myopia.

Methods: We utilized m⁶A methylation immunoprecipitation sequencing (MeRIP-seq) alongside RNA sequencing (RNA-seq) to investigate the levels of m⁶A modification and mRNA expression in the scleras of form-deprived myopic (FDM) guinea pigs. Subsequent bioinformatics analysis was performed to identify the enriched pathways and genes associated with m⁶A modification.

Results: Bioinformatic analyses indicated that hypermethylated mRNAs were predominantly associated with the calcium signaling pathway and may participate in extracellular matrix (ECM) remodeling. Through integrated analysis of MeRIP-seq and RNA-seq data, it was found that more than half of the differentially expressed modified genes (DEGs) exhibiting increased mRNA levels also showed an upregulation of m⁶A modification levels. These genes may play significant roles in the process of myopic scleral remodeling in response to elevated levels of methyltransferase METTL14.

Conclusion: This study highlights the role of m⁶A methylation, mediated by METTL14, in the regulating of key genes involved in calcium signaling and ECM remodeling during myopia progression. These findings suggest that targeting m⁶A modifications may could offer new therapeutic strategies for the treatment of myopia.

Purpose: To explore the protective effect and underlying mechanism of exogenous αA-crystallin (CRYAA), a molecular chaperone with antioxidant properties, in retinal ischemia-reperfusion (I/R) injury via modulation of the Nrf2/HO-1 signaling pathway.

Methods: In vivo, retinal I/R injury was induced in Sprague Dawley rats by transient intraocular pressure elevation, followed by intravitreal CRYAA administration. In vitro, human retinal microvascular endothelial cells (HRMECs) were exposed to H₂O₂-induced oxidative stress with or without CRYAA treatment. Oxidative markers (ROS, MDA, SOD), apoptosis (TUNEL, Caspase-3), and Nrf2/HO-1 pathway activation were evaluated via histopathology, biochemical assays, Western blotting, and flow cytometry. Nrf2 overexpression and siRNA knockdown were performed to validate pathway involvement.

Results: CRYAA attenuated retinal edema and structural disorganization in I/R rats, restore partial retinal blood flow, reduced ROS (p < 0.05) and MDA levels, restored SOD activity (p < 0.05), and suppressed apoptosis by downregulating Caspase-3 (p < 0.05). Mechanistically, CRYAA enhanced Nrf2 phosphorylation, nuclear translocation, and HO-1 expression (p < 0.05). Nrf2 overexpression amplified these effects, while Nrf2 silencing abolished CRYAA's protection, confirming pathway dependency.

Conclusions: Exogenous CRYAA mitigates retinal I/R injury by activating the Nrf2/HO-1 axis, reducing oxidative stress, and inhibiting apoptosis. These findings highlight CRYAA's therapeutic potential for ischemic retinal disorders and underscore Nrf2 as a critical mediator of its protective effects.

Purpose: The study aims to investigate the relationship between pancreatic β-cell function and macular vascular structure and blood flow in patients with type 2 diabetes mellitus (DM) without clinical signs of diabetic retinopathy (DR).

Methods: This prospective cross-sectional study enrolled 121 type 2 DM patients without clinical DR, representing a total of 240 eyes. The area under the C-peptide release curve (AUCC) derived from the oral glucose tolerance test, fasting serum C-peptide level and the updated Homeostasis Model Assessment (HOMA2) model were utilized to reflect pancreatic β-cell function. Insulin resistance (IR) was assessed by HOMA2 model. The macular vascular and blood flow parameters of patients were measured by optical coherence tomography angiography (OCTA). Separate Linear Mixed-Effects Models were employed to analyze the relationship between pancreatic β-cell function indicators and OCTA metrics.

Results: In separate multivariate models, AUCC, fasting serum C-peptide level, and HOMA2 estimates of β-cell function (HOMA2-B) each demonstrated a significant positive association with vessel density (VD) measures in the deep capillary plexus (DCP), including total DCP VD, parafoveal DCP VD, and perifoveal DCP VD.

Conclusions: The impaired pancreatic β-cell function is significantly associated with adverse macular vasculature alterations, suggesting that these vascular changes may occur prior to the clinical manifestation of DR in patients with compromised β-cell function. β-cell function markers might help identify patients at risk of early subclinical retinal microvascular changes.

Purpose: To investigate the causal relationship between age-related macular degeneration (AMD) and inflammatory bowel disease (IBD) by Mendelian randomization (MR) analysis.

Methods: The single nucleotide polymorphism data of IBD and AMD were obtained from the Integrative Epidemiology Unit (IEU) Open genome-wide association study database. MR analysis contained MR-Egger, weighted median, inverse variance weighted, simple mode, and weighted mode. Sensitivity analysis was executed to ensure the reliability of results, containing heterogeneity test, horizontal pleiotropy test, and leave-one-out analysis. Multivariable Mendelian randomization analysis was carried out to investigate potential confounding factors such as C-reactive protein, smoking, vitamin D deficiency. Genes corresponding to the instrumental variables (IVs) and functional enrichment analysis were executed.

Results: MR analysis showed a positive correlation between IBD and AMD (P < 0.05, OR > 1). Sensitivity analyses also did not reveal heterogeneity and horizontal pleiotropy. C-reactive protein, smoking, and vitamin D deficiency had no significant effect on AMD (P > 0.05). Genes corresponding to IVs were mainly associated with monocyte differentiation, cytokine receptor activity, etc., and act on signaling pathways such as Th17 cell differentiation, and there was a complex network of molecular-cell regulation.

Conclusion: Our study explored and demonstrated the causal relationship between IBD and AMD through MR analysis, which provided an important reference and direction for future research and treatment related to AMD.

Purpose: Primary open-angle glaucoma is characterized by trabecular meshwork cell injury and excessive extracellular matrix deposition. Given the established involvement of long non-coding RNAs in primary open-angle glaucoma pathogenesis, this study investigates the role and mechanism of long non-coding RNA H19 in mediating trabecular meshwork cell dysfunction and extracellular matrix production.

Methods: Hydrogen peroxide-treated human trabecular meshwork cells were used to establish in vitro primary open-angle glaucoma models. Cell viability and apoptosis were assessed via cell counting kit-8 and flow cytometry. Gene/protein expression of H19, Smad4, and extracellular matrix components (fibronectin, collagen I, and laminin) was evaluated by real-time quantitative polymerase chain reaction, Western blotting, and immunofluorescence. Subcellular H19 localization was determined by nuclear-cytoplasmic fractionation. The H19-miR-20a-5p-Smad4 regulatory axis was validated through luciferase reporter assays and rescue experiments across three characterized human trabecular meshwork cell strains.

Results: Hydrogen peroxide exposure induced concentration-dependent human trabecular meshwork cell injury and significantly upregulated H19 and Smad4 expression (p < 0.001). H19 knockdown attenuated oxidative damage, restoring viability (p < 0.001), reducing apoptosis (p < 0.001), and suppressing extracellular matrix deposition (p < 0.001). Mechanistically, H19 functioned as a competing endogenous RNA by binding miR-20a-5p, which targeted Smad4. Smad4 overexpression or miR-20a-5p inhibition abrogated H19 deficiency-mediated protection. Notably, H19 knockdown also reduced transforming growth factor-beta/Smad signaling (p < 0.001) while enhancing nuclear factor erythroid 2-related factor 2/heme oxygenase-1 antioxidant responses (p < 0.001).

Conclusion: Long non-coding RNA H19 facilitates hydrogen peroxide-induced human trabecular meshwork cell injury and extracellular matrix deposition primarily by orchestrating the miR-20a-5p/Smad4 axis, with additional modulation of transforming growth factor-beta/Smad and nuclear factor erythroid 2-related factor 2 pathways.