β-Amyloid Deposition and Functional Impairment in the Retina of the APPswe/PS1ΔE9 Transgenic Mouse Model of Alzheimer's Disease

PURPOSE. To determine whether beta-amyloid (A beta) deposition affects the structure and function of the retina of the APPswe/PS1 Delta E9 transgenic (tg) mouse model of Alzheimer's disease. METHODS. Retinas from 12- to 19-month old APPswe/PS1 Delta E9 tg and age-matched non-transgenic (ntg) littermates were single or double stained with thioflavine-S and antibodies against A beta, glial fibrilar acidic protein (GFAP), microglial marker F4/80, choline acetyltransferase (ChAT), and syntaxin 1. Quantification of thioflavine-S positive plaques and retinal layer thickness was analyzed semi-quantitatively, whereas microglial cell size and levels of F4/80 immunoreactivity were evaluated using a densitometry program. Scotopic electroretinogram (ERG) recording was used to investigate retinal physiology in these mice. RESULTS. Thioflavine-S positive plaques appeared at 12 months in the retinas of APPswe/PS1 Delta E9 tg mice with the majority of plaques in the outer and inner plexiform layers. Plaques were embedded in the inner plexiform layer strata displaying syntaxin 1 and ChAT. The number and size of the plaques in the retina increased with age. Plaques appeared earlier and in greater numbers in females than in male tg littermate mice. Microglial activity was significantly increased in the retinas of APPswe/PS1 Delta E9 tg mice. Although we did not detect neuronal degeneration in the retina, ERG recordings revealed a significant reduction in the amplitudes of a- and b-waves in aged APPswe/PS1 Delta E9 tg compared to ntg littermates. CONCLUSIONS. The present findings suggest that A beta deposition disrupts retinal structure and may contribute to the visual deficits seen in aged APPswe/PS1 Delta E9 tg mice. Whether A beta is involved in other forms of age-related retinal dysfunction is unclear. (Invest Ophthalmol Vis Sci. 2009;50:793-800) DOI:10.1167/iovs.08-2384