Exploring ethnic and racial differences in intraocular pressure and glaucoma: The Canadian Longitudinal Study on aging.

Purpose: To determine whether self-reported race/ethnicity is associated with intraocular pressure (IOP) and glaucoma and to explore whether any associations are due to social, behavioral, genetic, or health differences. Design: Cross-sectional analysis of population-based data. Methods: We used the Canadian Longitudinal Study on Aging Comprehensive Cohort, which consists of 30,097 adults aged 45-85 years. Race/ethnicity was self-reported. Corneal-compensated intraocular pressure (IOP) was measured in mmHg using the Reichert Ocular Response Analyzer. Participants were asked to report if they have ever had a diagnosis of glaucoma and whether they used eye care in the past year. A glaucoma polygenic risk score (PRS) was calculated. Logistic and linear regression models were used. Results: Black individuals had higher mean IOP levels (beta coefficient (ß) = 1.46; 95% confidence interval [CI], 0.62, 2.30) while Chinese, Japanese and Korean (ß = -1.00; 95% CI, -1.63, -0.38) and Southeast Asian and Filipino individuals (ß = -1.56; 95% CI, -2.68, -0.43) had lower mean IOP levels as compared to White individuals after adjustment for sociodemographic, behavioral, genetic, and health-related variables. Black people were more likely to report glaucoma as compared to White people after adjustment (odds ratio [OR] = 2.43; 95% CI, 1.27, 4.64). Conclusion: Racial and ethnic differences in IOP and glaucoma were identified. Adjusting for sociodemographic, behavioral, genetic, and health-related variables did not fully explain these differences. Longitudinal research is needed to further explore the reasons for these differences and to understand their relevance to disease pathogenesis and progression.

Alcohol Consumption, Genetic Risk, and Intraocular Pressure and Glaucoma: The Canadian Longitudinal Study on Aging.

Purpose: The purpose of this study was to examine the association of alcohol consumption with intraocular pressure (IOP) and glaucoma and to assess whether any associations are modified by a glaucoma polygenic risk score (PRS). Methods: Cross-sectional analysis of data from the Canadian Longitudinal Study on Aging Comprehensive Cohort, consisting of 30,097 adults ages 45 to 85 years, was done. Data were collected from 2012 to 2015. Alcohol consumption frequency (never, occasional, weekly, and daily) and type (red wine, white wine, beer, liquor, and other) were measured by an interviewer-administered questionnaire. Total alcohol intake (grams/week) was estimated. IOP was measured in mm Hg using the Reichert Ocular Response Analyzer. Participants reported a diagnosis of glaucoma from a doctor. Logistic and linear regression models were used to adjust for demographic, behavioral, and health variables. Results: Daily drinkers had higher IOP compared to those who never drank (ß = 0.45, 95% confidence interval (CI) = 0.05, 0.86). An increase in total weekly alcohol intake (per 5 drinks) was also associated with higher IOP (ß = 0.20, 95% CI = 0.15, 0.26). The association between total alcohol intake and IOP was stronger in those with a higher genetic risk of glaucoma (P for interaction term = 0.041). There were 1525 people who reported being diagnosed with glaucoma. Alcohol consumption frequency and total alcohol intake were not associated with glaucoma. Conclusions: Alcohol frequency and total alcohol intake were associated with elevated IOP but not with glaucoma. The PRS modified the association between total alcohol intake and IOP. Findings should be confirmed in longitudinal analyses.

Inverse Association of APOE ε4 and Glaucoma Modified by Systemic Hypertension: The Canadian Longitudinal Study on Aging.

Purpose: Studies examining the apolipoprotein E (APOE) ε4 allele and glaucoma are inconsistent, which could be due to interactions with other factors. We examined the relationship between the APOE ε4 allele and glaucoma and intraocular pressure in a large, population-based random sample and explored whether the APOE ε4 allele interacted with systemic hypertension. Methods: Data came from the Canadian Longitudinal Study on Aging, a population-based study that included 24,655 adults ages 45 to 85 years old in the European ancestry cohort. APOE genotypes were derived from single-nucleotide polymorphisms rs429358 and rs7412. Participants were asked about a prior diagnosis of glaucoma from a doctor. Corneal compensated intraocular pressure (IOP) was measured using the Reichart Ocular Response Analyzer. Results: Having an APOE ε4 allele was associated with a lower odds of glaucoma after adjusting for age, sex, IOP, and the top 10 population structure principal components (odds ratio [OR] = 0.83; 95% confidence interval [CI], 0.69-0.98; P = 0.033). A novel statistically significant interaction was found in that having an APOE ε4 allele was only associated with glaucoma in those without systemic hypertension (OR = 0.62; 95% CI, 0.46-0.85) although it was not associated in those with it (OR = 0.97; 95% CI, 0.79-1.21) (interaction term P value = 0.017). APOE ε4 was not associated with IOP (ß = -0.01; 95% CI, -0.13 to 0.10). Conclusions: Evidence increasingly points to the APOE ε4 allele having protective benefits against glaucoma, but this association was limited to those without systemic hypertension. Further research is needed to understand the biological mechanisms for these findings and the treatment potential they hold.

The Rb/E2F axis is a key regulator of the molecular signatures instructing the quiescent and activated adult neural stem cell state.

Long-term maintenance of the adult neurogenic niche depends on proper regulation of entry and exit from quiescence. Neural stem cell (NSC) transition from quiescence to activation is a complex process requiring precise cell-cycle control coordinated with transcriptional and morphological changes. How NSC fate transitions in coordination with the cell-cycle machinery remains poorly understood. Here we show that the Rb/E2F axis functions by linking the cell-cycle machinery to pivotal regulators of NSC fate. Deletion of Rb family proteins results in activation of NSCs, inducing a transcriptomic transition toward activation. Deletion of their target activator E2Fs1/3 results in intractable quiescence and cessation of neurogenesis. We show that the Rb/E2F axis mediates these fate transitions through regulation of factors essential for NSC function, including REST and ASCL1. Thus, the Rb/E2F axis is an important regulator of NSC fate, coordinating cell-cycle control with NSC activation and quiescence fate transitions.