Cholesterol synthesis in the vertebrate retina: Effects of U18666A on rat retinal structure, photoreceptor membrane assembly, and sterol metabolism and composition

摘要: Treatment of neonatal rats with U18666A, an inhibitor desmosterol Δ24-reductase, results in accumulation (Δ5,24) and depletion cholesterol (Δ5) various bodily tissues also causes cataracts. We evaluated the effects U18666A on sterol composition, de novo synthesis, histological structure retina. Neonatal Sprague-Dawley were injected subcutaneously (15 mg/kg, olive oil) every other day from birth through 3 wk age; parallel, control received oil alone. At 21 d, treated groups each subdivided into two groups: one group was intravitreally [3H]acetate; retinas removed 20 h later non-saponifiable lipids (NSL) analyzed by radio-high-performance liquid chromatography. The [3H]leucine; 4 d later, eye animal light electron microscopy microscopic autoradiography, while contralateral rod outer segment (ROS) membranes prepared thereform sodium dodecyl sulfate-polyacrylamide gel electrophoresis/fluorography. In group, Δ5/Δ5,24 mole ratio ca. 1.0, >88% NSL radioactivity Δ5,24; contrast, had >170, >80% Δ5. Retinal histology, ultrastructure, ROS renewal rates, rhodopsin synthesis intracellular trafficking comparable both animals. These suggest that can either substitute functionally for retina or it complement subthreshold levels synergism.