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A more recent version of this article appeared on February 1, 2009
 (Investigative Ophthalmology and Visual Science. )
© 2008 by The Association for Research in Vision and Ophthalmology, Inc.
doi:10.1167/iovs.08-2384
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Article

{beta}-Amyloid Deposition and Functional Impairment in the Retina of the APPswe/PS1{Delta}E9 Transgenic Mouse Model of Alzheimer’s Disease

Sylvia Eva Perez 1*, Stephen Lumayag 2, Beatrix Kovacs 3, Elliott J Mufson 4, and Shunbin Xu 2

1 Neurological Sciences, Rush University Medical Center, 1735 W Harrison St. # 300, Chicago, Illinois, 60612, United States
2 Neurological Sciences and Ophthalmology, Rush University Medical Center, chicago, Illinois, United States
3 Neurological Sciences and Ophthalmology, Rush University Medical Center, Chicago, Illinois, United States
4 Neurological Sciences, Rush University Medical Center, Chicago, Illinois, United States

* To whom correspondence should be addressed. E-mail: sylviapa69{at}hotmail.com.


  Abstract

Purpose. To determine whether {beta}-amyloid (A{beta}) deposition affects the structure and function of the retina of the APPswe/PS{Delta}1E9 transgenic (tg) mouse model of Alzheimer’s disease. Methods. Retinas from 12-19 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 (IPL) layers. Plaques were embedded in the IPL 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.

Key Words: Amyloid, retinal dystrophy, immunocytochemistry, tansgenic mice, microglia, visual deficits




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