Comprehensive Investigation of Functional and Structural Retinal Alterations in Ocular Albinism: A Study on CD-1 Mice

Abstract

Purpose : Albinism, a recessive genetic disorder affecting various species, manifests visually as low vision, photophobia, iris depigmentation, and retinal anomalies. Albino Swiss mice (CD-1) are widely used in research. This study aimed to investigate functional and structural retinal alterations in albino CD-1 mice specifically related to ocular albinism.

Methods : Ninety-two 15-week-old male CD-1 mice were utilized. Functional assessment employed full-field electroretinography (ERG flash), while in vivo retinal structure was examined using Spectral-Domain Optical Coherence Tomography (SD-OCT Spectralis). Immunohistochemistry (IHC) techniques on retinal sections analyzed cone structure (anti-Cone Arrestin), rod outer segments (anti-Rhodopsin), bipolar cells (anti-Protein Kinase C-α), ganglion cells (anti-Brn3a), microglia (anti-Iba-1), and macroglia (anti-GFAP).

Results : Photopic and scotopic ERG flash responses revealed that out of 92 animals, 39 exhibited normal vision (naïve), 44 lacked photopic vision (NOfot), 3 had low photopic and scotopic vision (BVfot+esc), and 6 were completely blind. Except for naïve mice, all groups displayed significant alterations in ERG wave amplitude and latency, completely abolished in the blind group. OCT revealed all retinal layers in all groups, except in blind mice where outer layers were absent. IHC analysis showed: i) altered cones and rods in NOfot and BVfot+esc groups, with total absence in blind mice; ii) normal bipolar cell structure across all groups; iii) no changes in ganglion cells between groups; iv) microglial study indicated activation in visually impaired groups, forming continuous rows in all layers; v) astrocyte study demonstrated thicker bands in NOfot and BVfot+esc groups compared to naïve mice, particularly pronounced in blind mice, featuring vertical GFAP+ columns corresponding to reactive Müller glia.

Conclusions : CD-1 mice may exhibit retinal alterations with a 60% incidence, crucial for research involving retinal studies. As a screening tool, non-invasive ERG is recommended before experiments to assess visual status.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.