Previous reports have suggested that the rate of de novo cholesterol s
ynthesis in the adult vertebrate retina is extremely slow. We investig
ated cholesterol biosynthesis in the adult rat retina in vivo, followi
ng intravitreal injection of [H-3]acetate. HPLC analysis of retinal no
n-saponifiable lipid extracts revealed co-elution of radioactivity wit
h endogenous cholesterol mass within 4.5 h post-injection. Incorporati
on of [H-3]acetate into cholesterol was markedly reduced by co-injecti
on of known inhibitors of the cholesterol pathway. In contrast to prev
ious results with retinas from other species, no radiolabel or mass co
rresponded to squalene, except in lipid extracts from retinas treated
with NB-598, a squalene epoxidase inhibitor. These results demonstrate
, for the first time, the capacity of the adult vertebrate retina to r
apidly synthesize cholesterol de novo.