Retinal Responses to Visual Stimuli in Interphotoreceptor Retinoid Binding-Protein Knock-Out Mice.

Interphotoreceptor retinoid-binding protein (IRBP) is an abundant glycoprotein in the subretinal space bound by the photoreceptor (PR) outer segments and the processes of the retinal pigmented epithelium (RPE). IRBP binds retinoids, including 11-cis-retinal and all-trans-retinol. In this study, visual function for demanding visual tasks was assessed in IRBP knock-out (KO) mice. Surprisingly, IRBP KO mice showed no differences in scotopic critical flicker frequency (CFF) compared to wildtype (WT). However, they did have lower photopic CFF than WT. IRBP KO mice had reduced scotopic and photopic acuity and contrast sensitivity compared to WT. IRBP KO mice had a significant reduction in outer nuclear layer (ONL) thickness, PR outer and inner segment, and full retinal thickness (FRT) compared to WT. There were fewer cones in IRBP KO mice. Overall, these results confirm substantial loss of rods and significant loss of cones within 30 days. Absence of IRBP resulted in cone circuit damage, reducing photopic flicker, contrast sensitivity, and spatial frequency sensitivity. The c-wave was reduced and accelerated in response to bright steps of light. This result also suggests altered retinal pigment epithelium activity. There appears to be a compensatory mechanism such as higher synaptic gain between PRs and bipolar cells since the loss of the b-wave did not linearly follow the loss of rods, or the a-wave. Scotopic CFF is normal despite thinning of ONL and reduced scotopic electroretinogram (ERG) in IRBP KO mice, suggesting either a redundancy or plasticity in circuits detecting (encoding) scotopic flicker at threshold even with substantial rod loss.

The role of acetaldehyde in human psychomotor function: a double-blind placebo-controlled crossover study.

BACKGROUND: Acetaldehyde, the first product of ethanol metabolization, is a biologically active compound, but the behavioral properties of acetaldehyde in humans are largely undefined. We investigated the acute effects of both alcohol and acetaldehyde on psychomotor functions related to automobile driving skills. METHODS: Twenty-four men were selected through genotyping; one-half had the ALDH2*1/*1 (active form) genotype and one-half had the ALDH2*1/*2 (inactive form) genotype. In a double-blind placebo-controlled crossover design, each subject was administered one of the following doses of alcohol: .25 g/kg, .5 g/kg, or .75 g/kg or a placebo in four trials that took place at 1-week intervals. Blood ethanol concentration (BEC) and blood acetaldehyde concentration (BAAC) were measured nine times, and psychomotor function tests (critical flicker fusion threshold, choice reaction time, compensatory tracking task, and digit symbol substitution test) were assessed seven times in total over 4 hours after study drug ingestion. RESULTS: After the consumption of alcohol, BEC was comparable in the two subject groups, whereas BAAC was significantly higher in subjects with ALDH2 *1/*2 than in those with ALDH2 *1/*1. The psychomotor performance of subjects with ALDH2*1/*2 was significantly poorer than that of subjects with ALDH2*1/*1. Significant correlations between psychomotor performance and both BEC and BAAC were observed. However, in the linear regression analysis, BAAC significantly predicted poorer psychomotor performance, whereas BEC was not associated with any measure of psychomotor function. CONCLUSIONS: Acetaldehyde might be more important than alcohol in determining the effects on human psychomotor function and skills.