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S. C. Mema, S. Kuny, P. Freund, D. Trischuk, F. Gaillard, I. M. MacDonald, Y. Sauve; Retinal Remodeling Precedes Cone Loss in the ELOVL4 Mouse Model of Age-Related Macular Degeneration (AMD). Invest. Ophthalmol. Vis. Sci. 2007;48(13):23.
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© ARVO (1962-2015); The Authors (2016-present)
In the elderly population of North America, AMD represents the primary cause of blindness and the etiology of AMD remains unknown. The recently developed ELOVL4 transgenic mouse model of AMD was used to elucidate changes in retina anatomy related to photoreceptor loss.
Retinas from ELOVL4 mice (line2 from K Zhang, Moran Eye Center, Utah) and age-matched wildtype (WT) littermates were studied immunohistochemically at 9 and 12 months of age.
There was a progressive loss of photoreceptors affecting primarily the rods, accompanied by a truncation of both rod and cone inner and outer segments. Dendrites from rod bipolar and horizontal cells were less numerous and shorter. In parallel, the outer plexiform layer (OPL) was thinner and the number of photoreceptor axon terminals (labeled with bassoon) was reduced. Horizontal cell bodies tended to be solely juxtaposed to the OPL in ELOVL4. Rod bipolar cell bodies had irregular orientations with some of their processes extending horizontally along the thin OPL. The respective pattern of choline acetyl transferase and calbindin labeled amacrine cells, including cell bodies and terminals, were respected. Müller cell reactivity (GFAP expression in radial processes) was evident throughout the retina, while it was confined to the extreme periphery in WTs. All these degenerative changes were more pronounced in center than periphery, with the exception of Müller cell reactivity, which followed a reversed pattern.
Our results indicate that photoreceptor loss in the ELOVL4 mouse model of AMD is accompanied by reactive changes throughout the retina including morphological alterations in horizontal and rod bipolar cells, paralleled with Müller cell reactivity. While mice do not have a macula, the retinal dystrophy seen in the ELOVL4 mouse is more pronounced in the center of the retina compared with the periphery, adding to its pertinence for the investigation of AMD etiology and potential treatments.
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