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FATP1 is involved in lipid transport into cells and in intracellular lipid metabolism. We showed previously that this protein interacts with and inhibits the limiting-step isomerase of the visual cycle RPE65. Here, we aimed to analyze the effect of  Fatp1 -deficiency  in vivo  on the visual cycle, structure and function, and on retinal aging. Among the  Fatp  family members, we observed that only  Fatp1  and  4  are expressed in the control retina, in both the neuroretina and the retinal pigment epithelium. In the neuroretina,  Fatp1  is mostly expressed in photoreceptors. In young adult  Fatp1 −/−   mice,  Fatp4  expression was unchanged in retinal pigment epithelium and reduced two-fold in the neuroretina as compared to  Fatp1 +/+   mice. The  Fatp1 −/−   mice had a preserved retinal structure but a decreased electroretinogram response to light. These mice also displayed a delayed recovery of the b-wave amplitude after bleaching, however, visual cycle speed was unchanged, and both retinal pigment epithelium and photoreceptors presented the same fatty acid pattern compared to controls. In 2 year-old  Fatp1 −/−   mice, transmission electron microscopy studies showed specific abnormalities in the retinas comprising choroid vascularization anomalies and thickening of the Bruch membrane with material deposits, and sometimes local disorganization of the photoreceptor outer segments. These anomalies lead us to speculate that the absence of  FATP1  accelerates the aging process.

Fatp1 Deficiency Affects Retinal Light Response and Dark Adaptation, and Induces Age-Related Alterations