Retinoid dynamics in vision: from visual cycle biology to retina disease treatments

Light perception is a biological process that facilitates a profound interaction between the external world and the internal functions of living organisms. It begins with the absorption of photons with specialized visual pigments that contain vitamin A-derived chromophores. The light energy triggers the photoisomerization of the visual chromophore, initiating a cascade of signaling events that ultimately convert light into electrical signals interpreted as vision. However, the sustainability of vision relies on the continuous supply of the visual chromophore, which is maintained through light-dependent and light-independent processes. The importance of these processes is underscored by numerous blinding retinal diseases linked to impaired regeneration of the chromophore. Thus, research into the molecular mechanisms of visual chromophore biosynthesis has not only deepened our understanding of the organization of visual systems but also uncovered the etiologies of these debilitating diseases. In this review, we synthesize recent progress in understanding the mechanisms responsible for visual chromophore biosynthesis. We examine biological targets, therapeutic strategies, and drug discovery efforts aimed at restoring or bypassing metabolic blockades in visual chromophore regeneration, and assess the progress of clinical trials evaluating the effectiveness of therapies for degenerative retinal diseases.