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D. Stopek, S. Majzoub, M. Le Lez, F. Labarthe; Chorioretinopathy in LCHAD Deficiency : The Role of Mitochondrial Oxidative Stress. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1416.
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Long-chain 3-hydroxyacyl CoA dehydrogenase (LCHAD) participates in the mitochondrial fatty acid oxidation. Genetic fatty acid oxidation defects induce cellular energetic deficiency, and thus early life threatening manifestations. An appropriate diet prevents those severe manifestations in organs that consume much fatty acid for their energetic needs. LCHAD deficiency is the only mitochondrial fatty acid oxidation deficiency to induce moreover a chorioretinopathy. The attempt consists in an atrophic degeneration predominating at the posterior pole and begins histologically at the level of retinal pigment epithelium. What is the pathogenesis of this specific chorioretinal degeneration ?
Reviewing of literature and biochemical mechanisms analysis were combined.
LCHAD deficiency chorioretinopathy appears linked to toxic accumulation of 3-hydroxyacyl-carnitine rather than mitochondrial energetic defect. 3-hydroxyacyl, carried by l-carnitine, is the only hydroxylated fatty acid of the pathway. It participates in mitochondrial oxidative stress. Moreover, 3-hydroxyacyl-carnitine could interfere with the peroxysomal metabolism of docosahexanoic acid (DHA) which is known to participate in retinal metabolism. Regarding the prevention of chorioretinopathy, appropriate energetic diet is not efficient. Administrations of l-carnitine and DHA have been tested with controversial results.
Chorioretinopathy in LCHAD deficiency points out the chorioretinal toxicity of 3-hydroxyacyl. Some clinical and histological analogies with age related macular degeneration (ARMD) lead to hypotheses whether 3-hydroxyacyl is an actor of mitochondria-based model of ARMD and retinal degeneration, based on retinal pigment epithelium mitochondrial DNA susceptibility to oxidative stress?
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