Abstract
Abstract: :
Purpose: Binding proteins are thought to be necessary for delivering retinoids to RPE cells and photoreceptors and particularly for steps in the visual cycle. Mice lacking RBP (RBP–/–) display impaired vision early in life that begins to normalize with sufficient dietary vitamin A intake, while IRBP–deficient (IRBP–/–) mice undergo an early retinal degeneration that deteriorates with age, although the rate of recovery of visual function after a photobleach was accelerated. Our aims were to determine whether the absence of both binding proteins (IRBP–/–RBP–/–) resulted in 1) additional impairments in visual function and 2) changes in 11–cis–retinal regeneration. Methods: We studied four age–matched (3–month–old) groups of mice (wild–type [WT], RBP–/– [R], IRBP–/– [I], and IRBP–/–RBP–/– [D]). Electroretinographic (ERG) analyses (n=10–12 each group) were performed. In a bleaching protocol, mice were sacrificed under six light conditions (dark–adapted overnight, following a 5 min intense photobleach, and 5, 15, 30 and 60 min in dark after a photobleach, n=12 each group), and eyecup retinaldehydes were assessed. Results: ERGs indicated that I and D mice have the lowest sensitivity to a bright light flash (37% and 33% of WT a–wave amplitude, respectively), with R having an intermediate response (84% of WT). Eyecups from dark–adapted R, I and D groups contained less total retinaldehyde than WT mice (72%, 66% and 60% of WT). The amount of 11–cis–retinal regenerated 60 min after the photobleach was 26%, 30%, 18%, and 23% of the dark–adapted values in WT, R, I, and D, respectively. Conclusions: Our data indicate that the absence of both binding proteins does not significantly exacerbate visual function relative to single knockout mice . The reduced total retinaldehyde content in the knockout groups suggests that the binding proteins facilitate retention of retinoids in the retina.
Keywords: retinoids/retinoid binding proteins • electrophysiology: non–clinical • retinal degenerations: cell biology