Spontaneous Achromatopsia-Like Phenotype in Albino Swiss CD-1 Mice: Retinocortical Dysfunction, Neurovascular Remodeling, and Glial Activation.

Abstract

Purpose: To characterize the functional, structural, vascular, genetic, and histologic correlates of spontaneous retinal electrophysiological phenotypes in male CD-1 mice to ensure accurate phenotyping in vision research.

Methods: Baseline full-field flash ERG (ffERG) was recorded in 205 male CD-1 mice. Subsets were evaluated using visual evoked potentials (VEP; n = 12), optical coherence tomography/optical coherence tomography angiography (OCT/OCTA) (n = 17), Gnat2 genotyping (n = 8), and quantitative immunohistochemistry (n = 5-6/phenotype) for cone arrestin, rhodopsin, PKCα (bipolar cells), Brn3a (ganglion cells), Iba1 (microglia), and GFAP (macroglia).

Results: FfERG identified three phenotypes: normal (n = 74), cone dysfunction (n = 126), and severe retinal dysfunction (n = 5). FfERG and VEP showed absent cone responses in cone dysfunction mice and complete response abolition in the severe group. OCT/OCTA revealed outer retinal thinning and deep capillary plexus remodeling in severe dysfunction, whereas the cone dysfunction mice retained overall structure. Genotyping confirmed Gnat2 mutations in affected groups. Histology confirmed isolated cone loss in cone dysfunction and combined rod-cone loss in severe dysfunction, both with increased glial activation. Brn3a+ ganglion cells were significantly reduced in both affected groups compared to in normal mice.

Conclusions: Spontaneous Gnat2-associated retinal dysfunction is common in CD-1 mice, causing photoreceptor loss, neuroinflammation, and ganglion cell reduction. Baseline electrophysiological screening is crucial when using this strain for vision research.