AIM To investigate the functions of microRNA-26a-5p (miR-26a-5p) in the high glucose (HG)-induced rat retinal Mu00FCller cells (rMC-1) apoptosis and its possible mechanism. METHODS rMC-1 cells were transfected with miR-26a-5p mimics or phosphatase and tensin homolog (PTEN) siRNA under HG conditions. Cell apoptosis was analyzed by propidium iodide (PI) and annexin u2164 fluorescein isothiocyanate (FITC) staining. PTEN/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway activation was assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot. Inflammatory cytokines, interleukin (IL)-1u03B2, IL-6, were measured by enzyme-linked immunosorbent assay (ELISA). The miR-26a-5p-PTEN interaction was validated by dual-luciferase assay. RESULTS HG significantly suppressed miR-26a-5p expression and induced apoptosis in rMC-1 cells. Overexpression of miR-26a-5p attenuated HG-induced apoptosis by directly targeting PTEN, as confirmed by dual-luciferase reporter assay, which demonstrated that miR-26a-5p directly binds to the PTEN 3u2019-UTR, resulting in a 50% reduction in luciferase activity (Pu0026lt;0.01). Consistent with this, miR-26a-5p overexpression downregulated PTEN expression, enhanced PI3K/Akt phosphorylation, and suppressed the secretion of IL-1u03B2 and IL-6 (all Pu0026lt;0.01). CONCLUSION Upregulation of miR-26a-5p protects rMC-1 from HG-induced apoptosis by targeting PTEN via regulating the PI3K/Akt pathway and inflammatory responses. miR-26a-5p may be a potential therapeutic target for diabetic retinal neurodegeneration.
AIM: To determine the annual trends and risk factors for delayed access to care in community hospitals across Central Thailand—an area with high occupational injury risk. METHODS: This retrospective cross-sectional study analyzed data from four community hospitals in Central Thailand over six years (October 1, 2018–September 17, 2024). Patients aged ≥20y with ocular injuries, identified via International Classification of Diseases-10 (ICD-10) codes, were included. Demographics, injury characteristics, and care-seeking behaviors were recorded. Delayed access was defined as presentation >24h post-injury. Linear and logistic regression models were used to identify associated risk factors. Annual fiscal trends were analyzed to assess year-to-year patterns in delayed healthcare access. RESULTS: Among 6571 ocular injury cases, 4034 (61.4%) were male, with median age 43y [interquartile range (IQR) 31–57y], and 3983 (79.3%) were manual laborers. Delayed healthcare access was observed in 2426 cases (36.9%). Significant risk factors included age ≥60y [aOR: 1.55; 95% confidence interval (CI): 1.32–1.82], visits to F2-level hospitals [adjusted odds ratio (aOR): 2.03; 95%CI: 1.73–2.38], and outpatient visits (aOR: 14.01; 95%CI: 12.18–16.12). In F2 hospitals, subgroup analysis revealed a U-shaped reduction in delayed healthcare access for ocular injuries during the COVID-19 pandemic (2019–2021), adjusted for age and gender. CONCLUSION: This first in-depth study of ocular injuries in Central Thailand's community hospitals found persistently high delayed presentations, with older age, F2 hospital visits, and outpatient department (OPD) attendance as key contributing factors. The trend during the COVID-19 pandemic highlights the important role of lower-tier community hospitals in providing prompt and accessible care for patients. Strengthening healthcare infrastructure and public awareness is essential to ensure timely care and reduce preventable vision-related complications.
AIM: To evaluate and compare the efficacy and safety of two treat-and-extend (T&E) regimens (2- and 4-week intervals, Δ2w and Δ4w) of intravitreal conbercept injections in patients with neovascular age-related macular degeneration (nAMD). METHODS: This 24-month prospective randomized controlled trial at the First Affiliated Hospital of Chongqing Medical University included patients with nAMD. Eyes were randomly assigned (1:1) to receive intravitreal conbercept (0.5 mg) with T&E regimens using 2- or 4-week interval adjustments (Δ2w and Δ4w groups). Key outcomes included best-corrected visual acuity (BCVA), central retinal thickness (CRT), subfoveal choroidal thickness (SFCT), superficial vascular density (SVD), deep vascular density (DVD), and large-medium vascular density (LMVD) within the 3 mm macular foveal region. The primary endpoint was the mean change in BCVA from baseline to the 2-year follow-up (noninferiority cutoff: 4 letters). RESULTS: Ultimately, 61 participants (68 eyes) completed the 2-year study. Baseline characteristics were similar between the two groups. At week 96, the mean number of injections was 11.17±1.13 in the Δ2w group (36 eyes, with the mean age of 70.42±9.31y) and 9.84±1.02 in the Δ4w group (32 eyes, with the mean age of 71.25±9.99y; P<0.001). The mean changes in BCVA were 5.19±6.58 and 5.91±5.51 letters (P=0.528), and Δ4w being noninferior to Δ2w (difference: 0.71 letters; 95%CI: -3.67 to 2.24). The mean changes in CRT were -118.97±106.97 and -134.98±128.77 μm (P=0.406), and the mean changes in SFCT were -30.03±17.48 and -32.55±22.73 μm (P=0.538), respectively. No significant intergroup differences in vascular densities were observed. Type 1 macular neovascularization had a higher baseline BCVA and required more injections than those with other macular neovascularization subtypes. CONCLUSION: Intravitreal conbercept injections administered via 2- and 4-week intervals show similar efficacy and safety. The reduced injection frequency in the Δ4w regimen may help lower the overall treatment burden, and individualized therapy based on nAMD subtypes may further optimize clinical outcomes.
AIM: To explore the regulatory effect of long non-coding RNA H19 on the Nod-like receptor protein 3 (NLRP3) inflammasome and its functional role in the progression of diabetic retinopathy (DR). METHODS: Wild-type and H19 knockout rats were subjected to a high-fat and high-sugar diet combined with streptozotocin injection to establish an in vivo diabetes mellitus (DM) model. In vitro, rat primary retinal microvascular endothelial (CP-R114) cells were cultured under high-glucose conditions to mimic the diabetic microenvironment. The MTS assay was performed to evaluate cell viability. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of indicators related to glucose metabolism, lipid metabolism, oxidative stress, and inflammation in rat retinal tissues and CP-R114 cells. Hematoxylin and eosin (HE) staining was applied to observe the pathological morphological changes in retinal tissues. qRT-PCR was conducted to quantify the mRNA expression of H19, S-adenosylhomocysteine hydrolase (SAHH), and S-adenosylmethionine-dependent methyltransferase 3 beta (DNMT3b) in rat retinas. Western blotting and immunofluorescence staining were further utilized to detect the protein expression of SAHH, DNMT3b, NLRP3, Caspase-1, and interleukin (IL)-1β in retinal tissues. RESULTS: In DM model rats, H19 knockout significantly improved glucose and lipid metabolic disorders and alleviated oxidative stress. Notably, H19 deficiency effectively ameliorated retinal tissue injury. The expression levels of intercellular cell adhesion molecule-1 (ICAM-1), vascular endothelial growth factor (VEGF), and pro-inflammatory factors were markedly downregulated in H19-silenced DM rats. Mechanistically, H19 knockout upregulated the expression of SAHH and DNMT3b, while inhibiting the expression of NLRP3 inflammasome-associated proteins in DM rats. Consistent with the in vivo findings, H19 silencing suppressed NLRP3 inflammasome activation and elevated SAHH and DNMT3b expression in high-glucose-stimulated CP-R114 cells. CONCLUSION: This study demonstrates that H19 knockout alleviates DR progression in diabetic rats by activating the SAHH/DNMT3b signaling pathway and inhibiting NLRP3 inflammasome activation. Therefore, targeting H19 represents a promising novel therapeutic strategy for the clinical treatment of DR.
AIM: To investigate the changes in corneal densitometry (CD) after small incision lenticule extraction combined with accelerated corneal cross-linking (SMILE Xtra) for correcting moderate to high myopia and to analyze their correlation. METHODS: In this non-randomized retrospective comparative study, participants who underwent surgery were enrolled in the standalone SMILE group and SMILE Xtra group, respectively. Preoperative and postoperative uncorrected visual acuity, spherical equivalent (SE), and CD values were recorded at 1, 3, 6, and 12mo. Measurements were taken in the central (0–2 mm), paracentral (2–6 mm), and peripheral (6–10 mm) zones, as well as in the anterior 120 μm, central, and posterior 60 μm layers of the cornea. A generalized linear mixed model (GLMM) was used to compare CD values between groups and at different time points, and the correlation between postoperative CD values and residual bed thickness (RBT) was analyzed. RESULTS: Totally 31 participants (62 eyes, mean age 20.32±2.76y) were in the standalone SMILE group and 28 participants (53 eyes, mean age 20.45±2.08y) in SMILE Xtra group. At 12mo postoperatively, there were no statistically significant differences in uncorrected visual acuity or SE between the two groups (P>0.05). Preoperative CD values in all regions showed no significant differences between groups (all P>0.05). In the central (0–2 mm) and paracentral (2–6 mm) zones, and the anterior, central, and total stromal layers, group, time, and interaction effects were all significant (all P<0.001). At 1, 3, and 6mo postoperatively, CD values in the SMILE Xtra group were significantly higher than those in the SMILE group within the 0–2 mm and 2–6 mm diameter ranges, as well as in the anterior, central, and total layers (all P<0.05). At 12mo postoperatively, CD values in the anterior layer remained significantly higher in the SMILE Xtra group compared to the SMILE group (P=0.007), whereas no statistically significant differences were observed in other diameter ranges or stromal layers (all P>0.05). Correlation analysis revealed that at 12mo postoperatively, CD values in all regions of both groups showed a significant positive correlation with RBT (all P<0.05), except for the anterior layer in the SMILE group, which showed no significant correlation with RBT (r=0.114, P=0.380). CONCLUSION: SMILE Xtra induces transient early increase in CD, primarily in the anterior and central layers. Although values stabilize or decline by 12mo postoperatively, the clinical significance of these long-term patterns requires cautious interpretation, considering the potential influence of post-surgical structural changes. Further research is necessary to fully elucidate the underlying contributions to these densitometric changes.
