ABSTRACT Carotenoids, a class of dietary lipids, play critical roles in vision as precursors of retinoids (vitamin A and its metabolites) and macular pigments. Emerging evidence suggests a beneficial interaction between carotenoids and retinoids in the retina. Carotenoids may prevent retinoids to undergo blue light triggered photochemical reactions that eventually can harm the photoreceptors and the adjacent retina pigment epithelium. However, our knowledge about this process is limited and meaningful progress in this research field has been hampered by a lack of suitable animal models. In recent years, our laboratory has established novel tools and reagents that allow us to address three innovative aims. In Aim 1, we will follow the hypothesis that blue light-dependent photo-isomerization of all-trans-retinal can trigger a cascade of events that eventually damage the photoreceptors. We will study the biochemistry of these reactions in the mouse retina and analyze whether chemical scavenging of retinaldehyde can prevent this pathology. For Aim 2, we have established a mouse model that accumulates lutein and zeaxanthin in the retina. The retina of these mice will allow testing of the protective role of carotenoids against light-induced retinal damage and oxidative stress in a small animal model with striking similarity to humans in anatomy, physiology, and genetics. In Aim 3, we will study the involvement of the carotenoid cleavage dioxygenase BCO2 in the metabolism of bisretinoids and oxidized carotenoids. These compounds form as side products of the visual process and can harm photoreceptors and the adjacent retinal pigment epithelium. We will study the biochemistry of the reaction and test whether BCO2 is a modulator of disease states that are characterized by the accumulation of bisretinoids. Understanding the chemistry and biology of carotenoids in vision is of substantial research interest because of the beneficial roles of these pigments for ocular health.