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Purpose: The ocular surface microenvironment changes with aging. However, it remains unclear if cellular senescence influences the ocular surface. We investigated the presence of p16 INK4a -expressing senescent cells in healthy human conjunctiva., Study Design: Clinical and experimental., Methods: Healthy conjunctival tissue samples were obtained from middle-aged and elderly subjects. RT-qPCR was performed to assess the expression of senescence markers CDKN2A (p16 INK4a ) and CDKN1A (p21 CIP1/WAF1 ) and immunostaining was performed to examine the expression of the senescence marker p16 INK4a , stem cell markers Ki67 and p63, tight-junction marker ZO-1., Results: Our study involved 19 conjunctival tissue samples (10 elderly and 9 middle-aged), mean age [elderly: 75.8 ± 3.7 years (72-81), middle-aged: 52.7 ± 7 years (38-59)], sex (elderly: 3 men, 7 women; middle-aged: 3 men, 6 women). The expression of p16 INK4a was significantly increased at the RNA level in the elderly compared to middle-aged (p < 0.05). Positivity rate of p16 INK4a was significantly elevated in the elderly (15.0 ± 7.8%) compared to middle-aged (0.2 ± 0.6%) (p < 0.05). Positivity rate of Ki67and p63 was significantly reduced in the elderly (1.7 ± 1.7% and 16.5 ± 9.5%) compared to middle-aged (3.9 ± 1.8% and 24.7 ± 5.7%) (p < 0.05). ZO-1 expression was reduced in tissue samples showing p16 INK4a -positivity but retained in tissue samples in which p16 INK4a was undetectable., Conclusions: Senescent cells accumulate with age in the conjunctival epithelium, accompanied by a decrease in Ki67, p63 and ZO-1 expressing cells., (© 2024. Japanese Ophthalmological Society.)

Dry eye is a multifactorial and common age-related ocular surface disease. Dyslipidemia has been reported to be involved in meibomian gland dysfunction (MGD). However, it has not been clearly identified which lipid abnormality is responsible for MGD. In this systematic review and meta-analysis, we discuss how lipid profile changes with aging is responsible for MGD development. Methods. An article search was performed in PubMed, EMBASE, and Web of Science. Eleven studies involving dyslipidemia in patients with MGD were identified. Five out of eleven studies were further analyzed with meta-analysis. The preferred reporting items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines were followed. Study-specific estimates (prevalence of dyslipidemia in MGD patients) were combined using one-group meta-analysis in a random-effects model. Results. Meta-analysis revealed that high total cholesterol (TC) and high triglycerides (TG) were significantly associated with MGD prevalence, with odds ratios of 5.245 (95% confidence interval [CI]: 1.582–17.389; p < 0.001) and 3.264 (95% CI: 1.047–10.181; p < 0.001), respectively, but high low-density lipoprotein (LDL) and low high-density lipoprotein (HDL) were not identified. Systematic review found that the percentage of MGD patients with TC ≥ 200 mg/dL ranged from 20.0–77.6%, TG ≥ 150 mg/dL ranged from 8.3–89.7%, whereas, in the aged-match-adjusted controls, TC range of 200 mg/dL or higher and TG range of 150 mg/dL was 6.1–45.1% and 1.1–47.8%, respectively. The severity of MGD was higher with dyslipidemia. Conclusion. Dyslipidemia and higher TC and TG are significant risk factors for MGD. [ABSTRACT FROM AUTHOR]