Identification of susceptibility loci for light-induced visual impairment in rats

Abstract

Bright light exposure in animals results in the selective degeneration of the outer retina, known as "retinal photic injury" (RPI). The susceptibility to RPI differs among rat strains. WKY rats display susceptibility to RPI with extensive retinal degeneration observed in the sagittal eye specimen, whereas LEW strain rats are resistant to it, showing only slight or no degeneration. In the present study, we first established an ethological screening method using the Morris water maze to discern differential susceptibility among the living rats. WKY and LEW were crossed to produce the first filial generation (F₁) offspring. Maze-trained individuals were exposed to bright, white light. The screening test results demonstrated that the susceptibility to light-induced visual impairment in rats is a dominant Mendelian susceptibility trait, as F₁ rats were susceptible to visual impairment like WKY rats. Therefore, F₁ rats were backcrossed with recessive LEW to produce the first backcross offspring (BC₁). Subsequent recurrent backcrossing while selecting for the susceptibility, indicated a segregation ratio of ca. 24% in BC₁ and BC₂ generations, indicating the involvement of two or more genes in the susceptibility. Further, microsatellite analysis of BC₁-to-BC₄ individuals using microsatellite markers mapped two susceptibility loci on chromosome segments 5q36 and 19q11-q12, named RPI susceptibility (Rpi)1 and Rpi2, respectively. This study provides an insight into mechanisms underlying differential susceptibility, which could help decipher the mechanism underlying the onset/progression of human age-related macular degeneration.

Keywords: Backcross; Morris water maze; Retinal photic injury; Strain difference; Susceptibility loci.