Clinical and Microscopic Characterization of Ocular Findings in Tg2576 ßAPP-Transgenic Mice

Abstract

Abstract: : Purpose: The Tg2576 ß-amyloid precursor protein-transgenic mouse is one of the most widely used transgenic models of Alzheimer's-like ß-amyloidosis. This mouse develops senile plaques and impairments in memory beginning around 9-months of age. The Tg2576 mice are continuously bred onto a hybrid C57/SJL background to maintain viability of the offspring and a robust phenotype. SJL mice are known to harbor a genetic abnormality associated with retinal degeneration. This study was conducted to characterize the ocular findings associated with the genetic background of the mice. Methods: Ophthalmic and microscopic examination of the eyes of 59 Tg2576 mice six months old or older and 18 of their nontransgenic littermates was performed. Results: A subset of both Tg2576 (25%) and nontransgenic littermates (22%) had marked retinal degeneration that was detectable as attenuation of retinal vessels and mottled depigmentation by ophthalmoscopic examination (estimated odds of the incidence of retinal degeneration in one group not statistically significantly increased over the other, p > 0.05). The retinal degeneration was characterized microscopically by a loss of photoreceptors, a finding consistent with impairment of vision. Posterior subcapsular cortical cataract was present in both transgenic (64%) and nontransgenic (44%) mice, and all darkly pigmented mice had numerous plump, melanin-laden cells scattered throughout the uvea. The odds of the presence of a posterior subscapular cortical cataract in Tg2576 mice were estimated to be 2.4 times as great as in the nontransgenic littermates; however this estimate was not statistically significantly different (p > 0.05) from even odds. Both Tg2576 mice (61%) and nontransgenic littermates (67%) had persistent hyaloid artery remnants. The estimated odds of the presence of persistent hyaloid artery remnants were slightly lower in Tg2576 mice relative to the transgenic littermates (0.776), but not statistically significantly different (p > 0.05) from even odds. Conclusions: Tg2576 mice and nontransgenic littermates have similar incidences of retinal and lenticular degeneration that is readily detectable by ophthalmoscopic examination at 6 months of age. These degenerative changes likely alter performance in visually guided behavioral tasks and funduscopic examination is a useful tool for detecting such changes in mice used as an animal model of Alzheimer's disease.

Keywords: animal model • retinal degenerations: hereditary • cataract