ACAD expression and role of mitochondrial fatty acid β‐oxidation in retinal pigment epithelium

Abstract

Mitochondrial fatty acid β‐oxidation (FAO) is the main energy providing pathway in the liver, heart and skeletal muscle particularly during fasting and prolonged exercise. Among several FAO defects, only patients with 3‐hydroxy‐acyl‐CoA dehydrogenase (LCHAD) and mitochondrial trifunctional protein (TFP) are affected with progressive retinopathy, a major concern and long‐term complication of such disorders. Pigmentary retinopathy causes progressive disturbances of retinal pigment epithelium (RPE) leading to accumulation of photo‐oxidized products by inhibiting the phagolysosomal degradation of the outer segment. Accumulated undigested lipids like hydroxylated fatty acids and proteins are thought to cause retinopathy in LCHAD deficiency. To decipher the pathogenetic mechanisms of retinopathy, we did incubation studies on cultured human RPE‐cells with various concentrations of palmitate and hydroxypalmitate with/without carnitine for 48 hrs. Thin cell sections under electron microscope revealed a massive accumulation of rod shaped long tubular formations that could be due to accumulation of complex oxylipids. Further immunoblotting showed robust expression of long and medium chain ACADs and HADH with scant expression of very‐long acyl‐CoA dehydrogenase. We thus conclude that other than TFP all other major FAO enzymes in the FAO pathway are expressed in human RPE cells.