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Cholesterol metabolism, oxysterols and retinal integrity
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Edité par CCSD -
International audience. The retina, as a part of the central nervous system, is particularly rich in lipids. Free cholesterol is found in plasma membranes where it participates in maintaining a structural organization required for proper visual transduction. Lack or excess of cholesterol has been shown to be neurotoxic in the brain and evidence indicate that it might also be the case in the retina. The retina exhibits a unique cholesterol metabolism based on endogenous synthesis and transport as well as on exchange with the systemic circulation via lipoproteins. Excess of cholesterol can also be eliminated after conversion into oxysterols, via CYP enzymes. In the retina, CYP46A1, that produces 24S-hydroxycholesterol (24S-OHC), is expressed in a specific type of neurons, targeted during glaucoma. Using primary cell cultures, we have shown that Müller cells, the major glial cells of the retina, were able to adjust their cholesterol metabolism in response to 24S-OHC exposure, highlighting the signaling role of 24S-OHC in neuron-glia communication. In addition, we have reported that the expression of CYP27A1, another retinal CYP enzyme, was modulated in a rat glaucoma model, along with the expression of other major actors of cholesterol metabolism. This was associated with a transient cholesterol overload in the retina. Drosophila making a powerful genetic model to study nervous tissue functionality, we have undertaken the retinal characterization of flies with a downregulated CYP27A1 ortholog mainly expressed in the drosophila retina and observed that they exhibit reduced eye size. Altogether, these data suggest that cholesterol conversion into oxysterols is crucial for cholesterol homeostasis and integrity of the retina.
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