Autophagy in the retinal pigment epithelium: a new vision and future challenges

Abstract

The retinal pigment epithelium (RPE) is a highly specialized monolayer of polarized, pigmented epithelial cells that resides between the vessels of the choriocapillaris and the neural retina. The RPE is essential for the maintenance and survival of overlying light-sensitive photoreceptors, as it participates in the formation of the outer blood-retinal barrier, phagocytosis, degradation of photoreceptor outer segment (POS) tips, maintenance of the retinoid cycle, and protection against light and oxidative stress. Autophagy is an evolutionarily conserved 'self-eating' process, designed to maintain cellular homeostasis. 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. In this review, we discuss selective autophagy and focus on the recent advances in our understanding of the mechanism of cell clearance in the RPE for visual function. Understanding how this catabolic process is regulated by both transcriptional and post-transcriptional mechanisms in the RPE will promote the recognition of pathological pathways in genetic disease and shed light on potential therapeutic strategies to treat visual impairments in patients with retinal disorders associated with lysosomal dysfunction.

Keywords: AMD; autophagy; lysosomal storage disease; mTOR; retinal pigment epithelium.

Fig. 1

The two main autophagy pathways in RPE cells. Simplified schematic of the network regulation to ensure the correct formation of all the components that take part in autophagy and LAP pathways.

Fig. 2

RPE autophagy dysfunction in AMD. Healthy RPE vs RPE in AMD. In normal RPE, an efficient autophagic flux and LAP processes occur. In aged RPE, oxidative stress and subsequent mTOR activation lead to lysosomal dysfunction and LAP impairment.