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: To study the regulatory effects and mechanisms of P2X7 receptors(P2X7R) on CD4⁺ regulatory T cells (Tregs) and pathogenic CD4⁺ T effector cells (Th1 cells).

Methods: In this research, an experimental autoimmune uveitis (EAU) mouse model was established to investigate the impact of P2X7R on Th1 and Treg immune responses.

Results: During the initial stage of EAU, appropriate activation of P2X7R leads to an enhanced Th1 immune response, including an increased proportion of CD4⁺ IFN-γ⁺ Th1 cells, increased production of cytokines tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ), and upregulation of transcription factor T-bet expression. Conversely, activation of P2X7R resulted in inhibition of Treg immune response, including a reduced proportion of CD4⁺Foxp3⁺Tregs, a decreased in cytokines transforming growth factor-beta (TGF-β) and interleukin-10 (IL-10), and a downregulation of the transcription factor Foxp3 expression. Extracellular signal-regulated kinase 1/2 (ERK1/2) signal and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) may be related to these effects. Interestingly, we observed that both Th1 and Tregs immune responses were reduced in P2rx^-/- mice compared with P2rx7^+/+ mice.

Conclusions: Our findings indicate that the promoting role of P2X7R in the early pathogenesis of EAU may be related to the contrary regulation of Th1 cells and Tregs, providing a new theoretical basis for the development of P2X7R targeted therapy.

Purpose: Keratoconus is a progressive corneal disorder characterized by thinning of the stromal layer. Corneal cross-linking (CXL), a widely used treatment, focuses on improving corneal strength by enhancing collagen cross-links. Alternative methods are being explored to increase the efficacy of CXL. This study aims to evaluate whether ozone, as a strong oxygen donor, can be utilized as an adjuvant or standalone cross-linking agent in an in vivo model.

Methods: The study involved 12 New Zealand albino rabbits, which were divided into three treatment groups, each receiving a different therapy: (1) CXL, (2) ozone, and (3) CXL combined with ozone (CXL+ozone). Corneal Visualization Scheimpflug Technology (Corvis ST), Anterior Segment Optical Coherence Tomography (AS-OCT), and Corneal Confocal Microscopy (CCM) measurements were performed post-procedure.

Results: Ozone therapy did not result in statistically significant differences compared to CXL in biomechanical parameters. Corvis ST measurements were not significantly different between groups. AS-OCT revealed full-thickness stromal brightness in the CXL+ozone group. CCM imaging showed hyperreflectivity limited to the anterior stroma in the CXL and ozone groups but distributed throughout the stroma in the CXL+ozone group. No adverse effects were observed.

Conclusion: Ozone therapy may enhance CXL efficacy and serves as a potential alternative. Its affordability, shorter duration, and comparable clinical outcomes make it particularly promising for resource-limited settings.

Purpose: Recent studies have demonstrated the effects of low-concentration atropine eye drops in slowing myopia progression. However, some studies have shown a rebound effect after treatment cessation. This study compares the rate of myopic progression following a rapid washout versus tapered cessation of 0.01% atropine.

Methods: This retrospective study included children treated with atropine 0.01% between 2015 and 2022. After 24 months of treatment, the gradual cessation (GC) group stopped atropine by reducing usage by one day per week each month until complete discontinuation. The prompt cessation (PC) group stopped treatment immediately. Subjective refraction was measured after cycloplegia, and axial length was assessed before drop instillation to compare myopia progression between the GC and PC groups during the 12 months following treatment cessation.

Results: Each group included 25 patients matched for age and spherical equivalent (SE) refractive error. The GC group had a mean age of 10.55 ± 1.19 years and the PG group 10.10 ± 1.7 years. The baseline SE refractive error averaged -4.33 ± 1.62D in GC and -4.50 ± 1.87D in PG. Mean follow-up was 12.4 ± 3.2 months (GC) and 12.2 ± 2.04 months (PG At follow up, the GC group had a mean SE refractive error progression of 0.21 ± 0.24 D and axial elongation of 0.15 ± 0.1 mm, while the PC group showed 0.43 ± 0.26 D and 0.25 ± 0.18 mm, respectively. However, linear mixed model (LMM) analysis revealed no statistically significant differences between the groups for axial length (p = 0.682) or SE (p = 0.541) change after treatment cessation.

Conclusions: The findings indicate that neither gradual nor prompt discontinuation of 0.01% atropine resulted in statistically significant differences in myopia progression. These results suggest no significant differences in myopia progression after treatment cessation between the two methods and provide no evidence of a rebound effect.

Purpose: This study was designed to assess retinal and choroidal microvasculature in acne patients using oral isotretinoin with optical coherence tomography angiography.

Materials and methods: One hundred and one eyes of 101 patients diagnosed with acne using isotretinoin and 105 eyes of 105 healthy subjects underwent retinal and choroidal assessment with the Triton swept-source deep range imaging optical coherence tomography device (Topcon Corp., Tokyo, Japan). The patients' superficial (VDs), deep (VDd), and choriocapillar (VDc) vascular densities were examined. Foveal avascular zones in the superficial (FAZs) and deep (FAZd) layers, as well as the central macular thickness (CMT) and subfoveal choroidal thickness (SFCT), were measured.

Results: In total, 32 males and 69 females were assessed. The mean duration of isotretinoin use was 81 days (range: 30-210 days). The cumulative dose of medication used was 2334 mg (range: 600-7200 mg). VDs and VDd showed no differences between the acne patients and the controls (p > 0.05). All sectors of the VDc values were significantly higher in the patients compared to the controls (p < 0.05). FAZs and FAZd were significantly higher in the patients compared to the controls (p = 0.048 and p = 0.041, respectively). The mean CMT significantly decreased in the patient group compared to the control group (p = 0.001), while the mean SFCT significantly increased (p = 0.002). The VDc superior values of the patients who used isotretinoin for more than 3 months were significantly higher than those of the patients who used the drug for less than 3 months (p = 0.01). We did not find any correlation with the total dose of isotretinoin, except for the nasal sector value of VDc (r = -0.199, p = 0.046).

Conclusions: Alterations of macular microvasculature were observed in acne patients using isotretinoin. In particular, a significant increment in choriocapillaris blood flow was detected.

Purpose: To assess the efficacy of ranibizumab-eqrn for neovascular age-related macular degeneration (nAMD), macular edema from retinal vein occlusion (RVO), and diabetic macular edema (DME) in eyes switched from reference ranibizumab.

Methods: Single-center, retrospective chart review of eyes which received at least three ranibizumab followed by at least three ranibizumab-eqrn injections over a two-year period. Eyes which were initially treated with alternative anti-VEGF agents were eligible for inclusion. Eyes that received surgery, laser, or intravitreal corticosteroids were excluded. Central foveal thickness (CFT) was measured at the initial and final visit in the ranibizumab and ranibizumab-eqrn groups for a subset of eyes. Primary outcome measures included best available visual acuity (VA) and CFT. Secondary outcome measures included number of intravitreal injections, follow-up time, and treatment interval. Analysis was performed using Python.

Results: 6233 Eyes from 4935 patients treated between June 6 2022 and June 6 2024 were included. 4692 (75.3%) eyes had nAMD, 1078 (17.3%) eyes had RVO, and 463 (7.4%) eyes had DME. Eyes received 7.1 ± 2.7 (total: 44500) ranibizumab injections over 10.5 ± 2.5 months. After switching, eyes received 5.8 ± 2.2 (total: 35840) ranibizumab-eqrn over 8.5 ± 1.7 months. Mean change in visual acuity was -1.0 ± 16.0 letters for ranibizumab vs. -0.6 ± 13.8 letters for ranibizumab-eqrn (p = 0.15). Mean change in CFT in a subset of 100 eyes was 0.81 ± 56.3 microns for ranibizumab vs. -7.2 ± 50.6 microns for ranibizumab-eqrn (p = 0.39). Mean injection interval increased from 8.3 weeks to 8.9 weeks in the ranibizumab vs. the ranibizumab-eqrn groups for all indications (p < 0.01).

Conclusions: In this large real-world study, eyes with nAMD, RVO, and DME switched to ranibizumab-eqrn from reference ranibizumab demonstrated similar efficacy.

Background: In order to explore the correlation between retinal microangiopathy and SARS-COV-2 infection, the clinical characteristics were summarized.

Methods: A retrospective cross-sectional study was conducted including outpatients who visited in the First Affiliated Hospital of Harbin Medical University in China from December 10, 2022 to January 31, 2023.Subjects underwent fundus color photography and macular optical correlation tomography to determine retinal microangiopathy.

Results: A total of 3666 outpatients were counted. And we have evaluated 41 patients developed COVID-19-associated retinal microangiopathy.27 patients had blurred vision; seven patients had dark shadow occlusion; one patient had visual deformation; eight patients had dry eyes, foreign body sensation and discomfort. Ocular pain occurred in two patients. High reflection signals were found in the outer nuclear layer of 32 patients (78.0%), in the external plexiform layer of 16 patients (39.0%), in the inner nuclear layer of 2 (4.9%), in the internal plexiform of four patients (9.8%), in the ganglion cell layer of 37 patients (90.2%). Fracture of the ellipsoid zone and interdigitation zone occurred in four patients (9.8%).

Conclusions: 1.12% of outpatients showed COVID-19-associated retinal microvascular changes. The actual incidence in the population was higher due to the limitations of the retrospective study.

Purpose: To investigate the effect of the P2X7 receptor (P2X7R) to the corneas and corneal nerves of rats with streptozotocin (STZ)-induced type 1 diabetes as well as the underlying mechanism.

Methods: In this study, male Wistar rats were first randomly divided into normal group (NL) and diabetes group (DM). After intraperitoneal injection of STZ, corneal perception, corneal fluorescein staining and the expression of P2X7R mRNA and protein in corneal tissues of NL and DM groups were detected before, 4, 6, 8, 12 and 16 weeks respectively. Then male Wistar rats were randomly divided into NL group, DM group and P2X7R inhibitor group (BBG). Start at 2 weeks after diabetes modeling, the BBG group was intraperitoneally injected with BBG every day. Corneal perception, corneal fluorescein staining, in vivo confocal microscopy, laser scanning confocal microscopy, corneal P2X7RmRNA levels, the mRNA levels of Brain-derived neurotrophic factor (BDNF), Glial cell-derived neurotrophic factor (GDNF), Nerve growth factor (NGF), Neuropeptide Y (NPY) and Growth associated protein-43(GAP-43) of corneal and trigeminal nerve were detected in the three groups at the 6th and 8th week.

Results: The mRNA and protein expression of P2X7R was significantly increased as early as 6 weeks after STZ injection and then showing a downward trend, but the corneal perception and corneal fluorescent staining continued to worse. Inhibition of P2X7R activation increased corneal sensitivity, ameliorated corneal epithelial damage, improved corneal subbasal nerve plexus density and length, increased the expression of BDNF in the trigeminal nerve and increased the expression of NPY in the corneal and trigeminal nerves.

Conclusions: The increase of P2X7R expression of diabetic rats was not synchronized with the gradually aggravated corneal injure. Inhibition of P2X7R activation can alleviate diabetes-associated corneal injury, regulate the expression of related neurotrophic factors and neuropeptides, and improve the corneal subbasal nerve plexus.