Current Eye Research最新文献

Purpose: This study aimed to elucidate the role of Src-homology 2 domain-containing inositol-5-phosphatase 1 (SHIP-1) in modulating immune responses in experimental allergic conjunctivitis (EAC) and to assess its therapeutic potential.

Methods: A short ragweed (SRW)-induced EAC mouse model was treated with subconjunctival injections of the SHIP-1 activator AQX1125 (3 mM/5 μL/eye) or antagonist 3AC (0.2292 μmol/5 μL/eye) every other day. Clinical symptoms were scored periodically, and conjunctival tissues were collected on days 1, 7, and 14 for histopathological (H&E staining) and immunofluorescence analyses. Protein expression in ocular tissues was evaluated by Western blotting, and immune cell profiles in the spleen were characterized by flow cytometry.

Results: Compared to 3AC, AQX1125 markedly attenuated ocular symptoms and reduced disease duration. Histopathological evaluation revealed diminished inflammatory cell infiltration in AQX1125-treated mice, whereas 3AC exacerbated infiltration. Immunofluorescence demonstrated reduced CD4⁺ T cell recruitment and enhanced SHIP-1 expression in the AQX1125 group at days 7 and 14. Western blot analysis showed upregulation of CCR7 alongside downregulation of PIP3, p-AKT, and p-mTOR in AQX1125-treated mice, while 3AC exerted opposing effects. Additionally, 3AC increased splenic CD4⁺ T cell populations at days 7 and 14 post-treatment.

Conclusion: SHIP-1 activation may represent a promising therapeutic approach for EAC, potentially through suppression of pathogenic CD4⁺ T cell migration and modulation of the PI3K/AKT/mTOR signaling pathway. These findings underscore the anti-inflammatory properties of SHIP-1 activators in allergic conjunctivitis.

Introduction: Retinopathy of prematurity (ROP) is a leading cause of childhood blindness, characterized by hypoxia-driven pathological retinal neovascularization. Current treatments, such as laser therapy and anti-VEGF drugs, carry significant risks, highlighting the need for safer preventive strategies. This study investigates the role of Pannexin-1 (Panx1) in the pathogenesis of ROP and explores its potential as a therapeutic target by modulating the HIF-1α/VEGF pathway.

Methods: Human retinal microvascular endothelial cells (HRMECs) were obtained from fetal eyes at 26-32 weeks gestational age, with ethical approval from the Guangdong Women and Children Hospital (No: 202201258). Retinal tissue was digested using 25 g/L trypsin and cultured in DMEM/F12 medium supplemented with 100 g/L fetal bovine serum (FBS). Transcriptomic sequencing libraries were prepared using the TruSeq stranded total RNA kit, and sequencing was conducted on the Illumina 6000 platform. Differentially expressed genes (DEGs) were identified (p < 0.05, |log₂FC| > 1). Validation experiments included rt-qPCR, Western blotting, and CCK-8 assays. Statistical analysis was performed using SPSS 24.0 and R v4.1.2, with DEG analysis conducted via the limma package.

Results: Transcriptomic sequencing revealed 567 differentially expressed mRNAs(345 upregulated, 222 downregulated) and indicated a significant upregulation of Panx1 expression in the ROP group compared to controls. Rt-qPCR and Western blotting confirmed hypoxia-induced overexpression of Panx1. Probenecid (PBC) treatment inhibited the hypoxia-driven upregulation of Panx1, HIF-1α, and VEGF at both mRNA and protein levels. CCK-8 assays showed that hypoxia significantly impaired HRMEC proliferation (24h: p < 0.05; 48h: p < 0.001), and PBC further suppressed this effect (p < 0.0001).

Conclusion: Panx1 inhibition (via PBC) suppresses the HIF-1α/VEGF signaling pathway and reduces hypoxia-induced endothelial cell proliferation, providing a novel preventive strategy for ROP.

Purpose: Anti-vascular endothelial growth factor (anti-VEGF) drugs have limitations in the treatment of neovascular age-related macular degeneration (nAMD). This study aims to evaluate the efficacy and safety of radiotherapy combined with anti-VEGF therapy versus anti-VEGF monotherapy in the treatment of nAMD.Methods: This systematic review and meta-analysis (PROSPERO registration number: CRD420251010811) searched PubMed, Embase, Cochrane, Web of Science, LILACS, ISRCTN registry, and ClinicalTrials.gov up to February 25, 2025. Two radiotherapy modalities were analyzed: epimacular brachytherapy (EBM) and stereotactic radiotherapy (SRT). The primary outcome was the proportion of participants who lost more than 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters at 12 and 24 months. A total of four studies were included, yielding 7 articles for meta-analysis.

Results: For EBM combined with anti-VEGF therapy, compared with anti-VEGF monotherapy, there was a higher risk of losing more than 15 ETDRS letters at 12 months (relative risk [RR] 2.36, 95% confidence interval [CI] 1.49-3.74) and 24 months (RR 2.39, 95% CI 1.68-3.39). The difference in best-corrected visual acuity (BCVA) was 0.10 logarithm of the minimum angle of resolution (logMAR) (95% CI 0.05-0.15) at 12 months and 0.17 logMAR (95% CI 0.13-0.21) at 24 months. For SRT combined with anti-VEGF therapy, there was a greater risk of losing more than 15 ETDRS letters at 24 months (RR 1.75, 95% CI 1.12-2.74) compared with anti-VEGF monotherapy; however, the SRT group required 2.10 fewer ranibizumab injections than the sham-irradiation group (mean difference [MD] -2.10, 95% CI -2.97 to -1.22).

Conclusion: Epimacular brachytherapy (EBM) combined with anti-VEGF therapy may worsen patient outcomes and increase the risk of adverse events. In contrast, stereotactic radiotherapy (SRT) combined with anti-VEGF therapy does not improve visual acuity but can reduce the frequency of anti-VEGF injections, potentially alleviating the treatment burden for patients with nAMD.

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.