Effects of Time-of-Day on the Expression of Autophagy Genes at the Different Stages of Age-Related Macular Degeneration-Like Retinopathy in Rat’s Retina

Abstract

Age-related macular degeneration (AMD) is a complex progressive eye disease, resulting in loss of central vision in the aging population. The senescence-accelerated OXYS rats reproduce the major signs of AMD. Autophagy is a cellular degradation pathway for the breakdown of cytoplasmic components. Defects in the autophagy are linked to aging and disease pathology. The purpose of this study was to determine the daily pattern of autophagy genes expression in the retina of young and old OXYS and Wistar control rats. Retina from 3-month and 21-month-old OXYS rats and Wistar rats were collected at ZT1, ZT8 and ZT16 in Zeitgeber time units, where ZT0 represents lights on (8:00) and ZT12 represents lights off (20:00). Levels of autophagy genes expression (Atg5, Atg7, Becn1, Gabarapl1, Nbr1, Map1lc3b, p62/Sqstm1, and Ulk1) were evaluated by quantitative reverse-transcription PCR. At the age of 21 months, OXYS rats had altered diurnal expression of three key autophagy genes (Atg7, p62/Sqstm1, and Ulk1) in the retina compared to age-matched Wistar rats and 3-month-old OXYS rats. No time-of-day or age-related changes in the expression of other autophagy genes were detected in control Wistar rats. Therefore, the regulation of autophagy is impaired in OXYS rats in late stages of retinopathy. Our study highlights the importance of the autophagy pathway in the pathogenesis of AMD and suggests that dysregulation of the autophagy daily rhythms accompanies the progression of AMD-like retinopathy.