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O. Payet, M. O. Pequignot, T. J. Guignard, L. Guillou, K. Chekroud, C. P. Hamel, P. Brabet; Towards a Role of FATP1 in the Retinal Pigment Epithelium Visual Cycle. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3525. doi: https://doi.org/.
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In vertebrates, the visual pigment is constituted by a protein, the opsin, and a chromophore, the 11-cis retinal. The latter is transformed in all-trans retinal when hit by a photon, and dissociates from the opsin. In order to regenerate the pigment, the all-trans retinoid is isomerized back through a cycle involving the retinal pigment epithelium, and the isomerization itself occurs through an isomerohydrolase complex, one of which key-enzyme is RPE65. We previously showed a strong interaction between RPE65 and FATP1 (fatty acid transport protein 1), an acyl-CoA synthetase. The question is now to understand if this interaction takes part of the retinoid cycle regulation. Our hypothesis is that FATP1 traps and activates a palmitate from the isomerization, facilitating the process in recycling the fatty acids into the membrane phosphatidylcholine.
FATP1-null mice have been obtained from collaboration with Andreas Stahl (Palo Alto, USA) and rose in our facility. Major deregulations of the visual cycle leads to retinal dystrophies in human. We then first let the mice getting old, to study the structure of the retina (photonic and electronic microscopy) and its function (ERG, pupillary reflex, PEV) along the time. In parallel, we developed techniques to evaluate the visual cycle efficiency (regeneration of the photopigment after bleach, light-damage susceptibility).
In 1-year-old mice, the structure of the -/- retina is normal. In electron microscopy, first experiments showed no differences in RPE and photoreceptor. ERG and pupillary reflex are also not different between -/- and +/+ mice. We now begin the evaluation of the visual cycle efficiency.
FATP1 absence does not induce retinal degeneration, suggesting that FATP1 is not a crucial element of the isomerohydrolase complex. However, more precise experiments are in progress to determine whether this protein can influence the kinetic of the visual cycle. If it is the case, FATP1 could be an interesting therapeutic target in the retinal degeneration due to a deregulation of the visual cycle.
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