Marked alteration of sterol metabolism and composition without compromising retinal development or function.

摘要: PURPOSE. To evaluate the consequences of altering retinal sterol metabolism and composition on development, histologic organization, electrophysiological function retina, under conditions that mimic biochemical hallmarks Smith‐Lemli‐Opitz (SLO) syndrome. METHODS. Pregnant Sprague‐Dawley rats were fed cholesterol-free chow containing AY9944 (treated group), an inhibitor 3b-hydroxysterol D 7 -reductase, from gestational day 6 through postnatal (P)28. Control animals same chow, but without AY9944. In addition, progeny in treated group injected subcutaneously every other birth to P28 with olive oil emulsion AY9944; control received alone. At various times, tissues harvested, their profiles analyzed by reversed-phase high-performance liquid chromatography. Companion eyes both groups examined histologically at P1. P28, evaluated electroretinography; then harvested for analysis companion subjected ultrastructural analyses. RESULTS. Treatment developing caused markedly abnormal accumulation 7-dehydrosterols severely reduced cholesterol levels all examined, relative animals. Despite this, exhibited normal development had no overt ocular defects or decrease electroretinographic function, up P28. CONCLUSIONS. These results unexpected, given known biophysical effects such alterations membrane properties profound dysmorphic cognitive abnormalities associated genetic -reductase have been linked SLO The suggest can substitute functionally retina perhaps act synergistically subthreshold residual allow cellular structure be achieved. (Invest Ophthalmol Vis Sci. 1999;40: 1792‐1801)