Current Eye Research最新文献

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.

Purpose: To evaluate the therapeutic effects of bakuchiol on clinical and histopathological outcomes in a rat model of corneal alkali burn.

Methods: Corneal alkali burns were induced in the right eyes of 35 male Wistar rats, which were randomized into five groups: control, carbomer, steroid, 0.14 mg/g bakuchiol, and 0.28 mg/g bakuchiol. Examinations were performed under stereomicroscopy with intraperitoneal ketamine anesthesia on days 0, 3, 7, and 14 to assess corneal epithelial defects and opacity; on day 14, corneal neovascularization was additionally evaluated. After the final examination, the eyes were enucleated, and the corneas were processed for hematoxylin-eosin and immunohistochemical staining. Epithelial necrosis, inflammatory cell density, corneal hemorrhage, stromal edema, and staining intensity for VEGF and TNF-α were semi-quantitatively scored.

Results: Bakuchiol treatment, particularly at 0.28 mg/g, significantly reduced corneal opacity, neovascularization, hemorrhage, and stromal edema compared with the steroid-treated group.

Conclusions: Bakuchiol demonstrated promising anti-inflammatory and anti-angiogenic effects and may represent a potential adjunctive treatment for corneal chemical injuries.

Purpose: When examining the ocular surface, patients are required to look straight ahead and the effects of vertical eye movement on tear film behavior are not considered despite it being natural and common to change gaze without blinking. This exposes parts of the bulbar conjunctiva previously covered by the eyelids and therefore not covered by the tear film during the preceding blink. This study investigates how the tear film behaves when presented with newly exposed areas of ocular surface due to vertical eye movements.

Methods: The tear film dynamics of a sequence of vertical open-eye gaze maneuvers (upgaze-downgaze) were studied in 15 participants with no ocular surface related complaints (OSDI <13) using the TearView infrared camera system. TearView detects the tear film based on natural infrared radiation emitted from the ocular surface. Interferometry was used to examine lipid layer behavior. In a subgroup (n = 3), eyelids were mechanically lifted using a finger to reveal bulbar conjunctiva.

Results: Vertical eye movements exposed bulbar conjunctiva not covered by the tear film during the preceding blink. The fully formed tear film reacted by spreading toward the newly uncovered ocular surface area, thereby recoating it. This also occurred when the eyelids were mechanically lifted to reveal ocular surface previously beneath the eyelids. No apparent flow occurred from the menisci onto the ocular surface.

Conclusions: The fully formed tear film is isolated from the meniscal tear and meibum reservoirs (a completely perched tear film). This tear film spontaneously spreads to cover ocular surface area that is newly exposed during vertical eye movements.

Purpose: Acanthamoeba keratitis (AK) is a sight threatening infection of the cornea caused by opportunistic pathogens belonging to the genus Acanthamoeba. AK is commonly associated with contact lens use, and treatments are currently limited and ineffective. As such, the emergence of antimicrobial resistance in Acanthamoeba poses a significant challenge to the management of AK. This study investigates the development of polyhexamethylene biguanide (PHMB) resistance, a frontline therapeutic, in Acanthamoeba trophozoites and explores potential cross-resistance to hexamidine and voriconazole.

Methods: Acanthamoeba castellanii trophozoites were exposed and maintained in PHMB starting at 2 µg/mL and increasing upon reaching confluence. Cells were subsequently exposed to incrementally higher doses of PHMB in a stepwise manner (2, 4, 5.5, and 7 µg/mL). When sustained growth under PHMB exposure was observed, morphology was assessed by imaging flow cytometry and susceptibility assays were performed by incubating resistant strains with PHMB, hexamidine, and voriconazole for 24 h, and viability determined using alamarBlue.

Results: Trophozoites surviving exposure at 2 µg/mL reached confluence within 11 days. Stepwise increases to 4 µg/mL, 5.5 µg/mL, and 7 µg/mL were achieved within 6-7 days at each stage. PHMB-resistant Acanthamoeba strains exhibited a 9-fold increase in resistance to PHMB relative to naïve cells, alongside significant cross-resistance to voriconazole (159-fold) and hexamidine (8.4-fold). No significant change in trophozoite or cyst morphology was observed relative to the naïve cell line.

Conclusions: These findings represent the first known laboratory-induced PHMB-resistant Acanthamoeba strains, raising concerns regarding the longevity of current therapeutic options and the potential for cross-resistance to alternative treatments. This highlights the need for clinical vigilance and further investigation into the molecular mechanisms of resistance to better inform treatment strategies.

Purpose: This study aims to elucidate the causal relationships and shared genetic architecture between metabolic-associated diseases and risk factors-including hypertension, type 1 diabetes (T1D), type 2 diabetes (T2D), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and body mass index (BMI)-and primary vision-threatening eye disorders, involving glaucoma, cataracts, refractive disorders, and age-related macular degeneration (AMD).

Methods: We analyzed genome-wide association study (GWAS) summary statistics from > 500 000 individuals of European ancestry in the FinnGen, UK Biobank, and MRC-IEU databases to ensure adequate sample size. Linkage disequilibrium score regression (LDSC) was applied to estimate genetic correlations, while two-sample Mendelian randomization (MR) was performed to assess causal effects. Furthermore, a bidirectional Mendelian Randomization was further conducted to examine the directionality of associations between hypertension and cataracts.

Results: This study was the first to reveal genetic correlations and causal effects of hypertension on cataracts, particularly senile cataracts. MR analysis provided evidence that hypertension is causally associated with an increased risk of cataracts, particularly senile cataract, whereas the reverse association was not supported. Additionally, LDL cholesterol was suggested as a protective factor for AMD, while HDL cholesterol was associated with an increased risk. The LDSC analysis also indicated a suggestive genetic correlation between T2D and both cataracts and glaucoma, but not for T1D.

Conclusion: This study provides comprehensive evidence of genetic correlations and potential causal relationships between metabolic-associated conditions and major eye diseases contributing to vision loss.