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J.A. Matsubara, J. Cui, K.H. Ashe; Role of Amuloid Toxicity in Experimental AMD: I. Localization of APP and Amyloid–Beta Deposits in the Retina of the Bi–transgenic Mouse TG2576 X TG1 . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3012.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: The bi–transgenic mouse, Tg2576 x Tg1, develops characteristic AD–like amyloid–ß (Aß) deposits in the brain because of the co–expression of a mutant human APP and a mutant human presenilin–1 transgene. The significant amyloid load in the CNS of this transgenic animal model makes it a potential candidate for studies of amyloid toxicity in the eye. However, to date, no study has reported the expression patterns in ocular tissue of Tg2576 x Tg1. The purpose of the study is to characterize APP and Aß expression in the eye of Tg2576 x Tg1, and correlate retinal Aß load with apoptosis of ganglion, photoreceptor and RPE cell types. Methods: Immunohistochemical localization of APP (22C11) and Aß (6F/3D) in eye tissue was undertaken in paraffin embedded 4 micra thick sections from Tg2576 x Tg1 mice (27, 19 or 8 months of age) that harbour a mutant APP transgene array and a mutant presenilin–1 gene. Results: Immunohistochemical detection of APP was present in all animals tested, with older animals displaying relatively stronger immunoreactivity compared to younger ones. APP immunoreactivity was present in the cytoplasm of the retinal ganglion cell, retinal cells of the inner nuclear layer and the RPE cell. Extracellular Aß deposits, located in the nerve fiber layer above the retinal ganglion cell layer, were present in the retina of the 27–month, but not the 8–month old transgenic animal. Conclusions: Both neuronal and retinal pigment epithelial cell types in the retina of the bi–transgenic mouse, Tg2576 x Tg1, overexpress APP with age. Extracellular Aß deposits are present in the nerve fiber layer overlying the ganglion cell layer. Of interest in this study is the demonstration that the RPE cell expresses APP in an age–dependent manner. The Tg2576 x Tg1 mouse may be useful as an animal model to study the role of amyloid toxicity in age–related degenerative eye diseases such as AMD.
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