Dysregulation of lipid metabolism on photoreceptor function and viability : The role of FATP genes in Drosophila and mice models – LipidinRetina

Inherited retinal degenerative diseases constitute a major cause of vision loss in humans. Retinitis pigmentosa and macular degeneration (MD) are the two main classes of retinal diseases. They are characterized by the loss of rod and cone photoreceptor (PR) cells leading to progressive blindness. Most monogenic forms of retinitis pigmentosa and MD are associated with genes expressed in PR or retinal pigment epithelial (RPE) cells where they encode proteins that are critical for PR structure, function and survival. Specific cellular processes and biochemical pathways implicated in retinopathies include: phototransduction, visual cycle, PR development, morphogenesis, cellular metabolism, protein folding, among others. Lipid metabolism is of major importance for retina integrity and its dysregulation can lead to retinopathies. Lipid disorders have been implicated in macular degeneration such as the Age-Related Macular Degeneration (AMD) and Stargardt disease.
Partner 1 has found that loss of function mutation in fatp (fatty acid transport protein) gene leads to PR loss in Drosophila and partner 2 has identified FATP1 as a potential regulatory component of the visual cycle in mammals. In the following four specific tasks, we propose to 1) Coordinate the project; use mouse FATP and Drosophila fatp mutants to study in 2) the roles of Fatp genes in PR function and survival, 3) examine the roles of Fatp genes in the visual cycle, and 4) investigate the role of Fatp genes in lipid metabolism in the retina (Partners 1, 2 and 3). All together our proposal will help elucidating the mechanisms by which a lipid dysregulation leads to PR degeneration and retinal pathology.