Morphometric analysis of susceptibility to retinal photic injury in rats: A triphasic severity classification based...

To investigate the anatomical and genetic associations with retinal photic injury (RPI), we integrated topographical analysis with our previously reported Morris water maze (MWM) data. Parental strains (WKY and LEW), first filial generation (F₁), and backcross (BC) offspring were used to analyze various degenerative phenotypes. Using our newly developed "geodesic length morphometry," we quantified the entire retinal arc length (10.79 ± 0.46 mm) and the physical extent of light-induced retinal degeneration in sagittal sections. By aligning the degeneration extent across male and female parental, F₁, and BC₁ populations (total n = 77) with swimming time (ST) in the MWM test, RPI severity was classified into three distinct phases. The retinal lesion consistently encompassed an epicenter 2.15 mm superior to the optic nerve head (ONH) and showed a characteristic spatial distribution. Unless the inferior lesion edge crossed a point 0.98 mm inferior to the ONH, MWM performance remained normal with a short ST. In many individuals with prolonged ST (≥10 s), the lesion crossed a point 1.95 mm inferior to the ONH. When the lesion edge existed between these boundaries, ST varied widely. Therefore, the 1.95-mm boundary represented a critical threshold for the retinal region necessary for lateral vision and spatial navigation. Genotypic analysis of 34 BC₄ individuals confirmed that the WKY-derived Rpi1 locus strongly influenced RPI susceptibility, modulating whether degeneration surpassed the critical thresholds. Overall, the putative Rpi1 locus affects the spatial expansion of retinal lesions, yielding a critical threshold between the preservation and decline of spatial-navigational competence.