The endosomal sorting complex required for transport (ESCRT) machinery plays a key role in the repair of damaged plasma membranes with puncta form and removes pores from the plasma membrane in regulated cell death, apoptosis, necroptosis, pyroptosis, ferroptosis, and autophagy. ESCRT-I overexpression and ESCRT-III-associated charged multivesicular body protein (CHMP) 4B participate in apoptosis, and the ESCRT-1 protein TSG 101 maintains low levels of ALIX and ALG-2 and prevents predisposition to apoptosis. The ESCRT-III components CHMP2A and CHMP4B are recruited to broken membrane bubble sites with the requirement of extracellular Ca²⁺, remove membrane vesicles from cells, and delay the time required for active MLKL to mediate necroptosis, thus preserving cell survival. CHMP4B disturbed pyroptosis by recruiting around the plasma membrane neck to remove the GSDMD pores and preserve plasma membrane integrity depending on Ca²⁺ influx. The accumulation of the ESCRT-III subunits CHMP5 and CHMP6 in the plasma membrane is increased by the classical ferroptosis activators erastin-1 and ras-selective lethal small molecule 3 (RSL3) upon cytosolic calcium influx and repairs the ferroptotic plasma membrane. ESCRT-III- and VPS4-induced macroautophagy, ESCRT-0-initiated microautophagy. ESCRT-I, ESCRT-II, ESCRT-III, ALIX, and VPS4A are recruited to damaged lysosomes and precede lysophagy, indicating that ESCRT is a potential target to overcome drug resistance during tumor therapy.

Aims: To evaluate the potential causal role of sleep traits (STs) on diabetic retinopathy (DR). Methods: The cross-sectional study included 23,851 patients with type 2 diabetes from the UK Biobank and used multivariate logistic models to investigate the observational association between STs and DR. Genetic correlation analysis and two-sample Mendelian randomization (MR) were conducted using ST data from the UK Biobank and DR data from the FinnGen consortium to investigate the genetic and causal associations between STs and DR. Results: Patients who experienced daytime sleepiness often/all of the time had a higher risk for DR (OR: 1.40; 95% CI, 1.09–1.79; p = .008) compared with those who sometimes/never/rarely experienced daytime sleepiness. Genetic correlations between several STs and DR were detected by cross-trait linkage disequilibrium score regression. MR suggested a causal effect of self-reported daytime sleepiness (OR: 4.08; 95% CI, 1.44–11.61; p = .008), and accelerator-derived sleep duration (OR: 0.73; 95% CI, 0.54–0.98; p = .036) and sleep efficiency (OR: 0.54; 95% CI, 0.36–0.80; p = .002) on DR. Conclusions: STs may have a potential causal role for DR. Attention should be paid to the STs of patients for better prevention and treatment of DR.

Excessive artificial light at night (ALAN) disrupts circadian rhythms and may accelerate ocular aging; however, personal objective dosimetry data linking evening light exposure to specific age-related eye diseases (AREDs) remain sparse. The objective of the study is to determine whether personal high-intensity light exposure during the evening transition window (20:00–23:30) is associated with the risk of incident age-related macular degeneration (AMD), cataracts, and glaucoma. This prospective cohort study utilized data from the UK Biobank. Participants (n = 82,826) were monitored for 7 days via wrist-worn accelerometers equipped with high-resolution light sensors between 2013 and 2015. Individuals with baseline eye diseases were excluded. Average light intensity (lux) during the evening transition period (20:00–23:30) was categorized by percentiles (top 10% threshold ≈1000 lx). Incident AMD, cataract, and glaucoma were identified through linked hospital inpatient records and death registries using ICD-9 and ICD-10 codes. Among 82,826 participants, 6058 incident ARED cases occurred during a median follow-up of 7.85 years. Evening light exposure exceeding 1000 lx (top 10%) was significantly associated with increased hazards of incident AMD (HR, 1.31; 95% CI, 1.06–1.62), cataract (HR, 1.18; 95% CI, 1.08–1.30), and primary open-angle glaucoma (POAG) (HR, 1.47; 95% CI, 1.07–2.03). Significant time–response relationships were observed, with per-hour exposure to > 2250 lx further elevating the risk of overall AREDs (HR, 1.10; 95% CI, 1.04–1.16) and POAG (HR, 1.18; 95% CI, 1.04–1.35). High-intensity artificial light in the evening is an independent, modifiable risk factor for major ocular aging pathologies. Graphical Abstract The alternative text for this image may have been generated using AI.

Age-related macular degeneration (AMD) is the leading cause of severe vision loss in elderly individuals aged >55 years in developed countries [1]. Approximately 196 million individuals, or 8.69% of the global population, are affected by AMD. With the increase in life expectancy and population ageing, this number is expected to rise to 288 million by […]