Accepted_test

Age-related macular degeneration (AMD) is a complex neurodegenerative eye disease, resulting in severe loss of central vision in the aging population. AMD pathogenesis is not completely known, but strongly associate with autophagy disruption. Autophagy is a conserved cellular degradation pathway for the breakdown of cytoplasmic components: damaged proteins and organelles. Besides a housekeeping function, autophagy is crucial for response to the stress. Defects in the autophagy are linked to aging and disease pathology. Circadian rhythms are a hallmark of physiology, but how such daily rhythms organize cellular catabolism is poorly understood. The retina has an own circadian system in that all retinal cells have their own oscillators which integrated for the rhythmic regulation of retinal physiology and function. In disease states, dysregulation of the retinal circadian rhythms might further exacerbate the development of retinopathy. The daily autophagy demands in the RPE require precise gene regulation for the digestion and recycling of intracellular and POS components in lysosomes in response to light and stress conditions. The time course of daily fluctuations in the levels of autophagy occurring in the photoreceptors and RPE has not been characterized, and the mechanisms underlying the dynamic regulation of autophagy in these cells remains unknown. The purpose of this study was to determine the daily pattern of autophagy genes expression in the retina of young and old Wistar and senescence-accelerated
OXYS rats which spontaneously reproduce the major signs of AMD: dystrophic
alterations of the RPE, thinning of the neuroretina, and impairment of choroidal
microcirculation.