S. H. Rho

Retinal pigment epithelial cells undergoing mitotic catastrophe are vulnerable to autophagy inhibition

The increased mitochondrial DNA damage leads to altered functional capacities of retinal pigment epithelial (RPE) cells. A previous study showed the increased autophagy in RPE cells caused by low concentrations of rotenone, a selective inhibitor of mitochondrial complex I. However, the mechanism by which autophagy regulates RPE cell death is still unclear. In the present study, we examined the mechanism underlying the regulation of RPE cell death through the inhibition of mitochondrial complex I. We report herein that rotenone induced mitotic catastrophe (MC) in RPE cells. We further observed an increased level of autophagy in the RPE cells undergoing MC (RPE-MC cells). Importantly, autophagy inhibition induced nonapoptotic cell death in RPE-MC cells. These findings indicate that autophagy has a pivotal role in the survival of RPE-MC cells. We next observed PINK1 accumulation in the mitochondrial membrane and parkin translocation into the mitochondria from the cytosol in the rotenone-treated RPE-MC cells, which indicates that increased mitophagy accompanies MC in ARPE-19 cells. Noticeably, the mitophagy also contributed to the cytoprotection of RPE-MC cells. Although there might be a significant gap in the roles of autophagy and mitophagy in the RPE cells in vivo, our in vitro study suggests that autophagy and mitophagy presumably prevent the RPE-MC cells from plunging into cell death, resulting in the prevention of RPE cell loss.

The Effects of Nocturnal Dip and Blood Pressure Variability on Paracentral Scotoma in Early Open-Angle Glaucoma

ABSTRACT Purpose: To evaluate the effect of nocturnal dip and blood pressure (BP) variability on paracentral scotoma in early open-angle glaucoma. Methods: The present study included 72 early normal-tension glaucoma (NTG) patients and 34 early primary open-angle glaucoma (POAG) patients. Nocturnal dip and weighted standard deviation (wSD) were determined by 24-hour ambulatory BP monitoring (24-hr ABPM). The mean deviation (MD) and pattern deviation (PD) were measured with visual field. Correlations between nocturnal dip and/or BP variability and paracentral scotoma were assessed using Student’s t-test, Pearson’s correlation test, and linear logistic regression analysis. Results: The systolic and diastolic nocturnal dip and paracentral scotoma occurrence demonstrated a statistically significant correlation in the early NTG group (systolic nocturnal dip: p=0.047, diastolic nocturnal dip: p=0.011). In the early NTG group, the subgroup with paracentral scotoma had a greater nocturnal dip than those patients without paracentral scotoma (systolic nocturnal dip: p=0.000; diastolic nocturnal dip: p=0.000). In the early NTG group, the subgroup with paracentral scotoma had higher wSD of SBP than the patients without paracentral scotoma (p=0.003). In the logistic regression analysis of the factors that can affect paracentral scotoma SBP dip and SBP, wSD appeared to significantly affect the occurrence of paracentral scotoma in the early NTG group. Conclusions: Early NTG patients with paracentral scotoma have nocturnal dip and large BP variability. Therefore, in early glaucoma patients, particularly in early NTG with paracentral scotoma, nocturnal dip and BP variability should be assessed with 24-hr ABPM.