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Valeriy Lyzogubov, Xiaobo Wu, Grant Kolar, Puran Bora, John Atkinson, Nalini Bora; Cd46 -/- Mouse as a Model of Dry-type Age-related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4591.
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In man and most mammals, CD46 (aka, membrane cofactor protein - MCP) is a widely expressed complement system regulator that primarily inhibits the alternative pathway and thereby protects host cells from complement attack. In rodents though, it was thought to be expressed solely on the inner acrosomal membrane of spermatozoa. However, we recently identified its expression by the neurosensory retina, RPE and choroid. This study was undertaken to determine if CD46 plays a role in AMD.
CD46 knock-out (Cd46 -/- ) mouse was prepared on a C57BL/6 background. The retina was analyzed at 2, 8 and 12 months by light and electron microscopy. Morphological signs of dry-type AMD were identified by analyzing the presence of degenerative changes in RPE cells, thickening of Bruch’s membrane, accumulation of deposits including formation of drusen-like structures and loss of photoreceptor cells. Measurements of these alterations and cell counting were performed using ImageJ program. They were performed in a “masked” fashion and the results compared to those in age- and sex-matched wild-type (WT) controls.
The % of RPE cells with condensation of chromatin and vacuolization of cytoplasm progressively increased (p<0.05) in Cd46 -/- mice at 2, 8 and 12 months compared to age-matched WT controls. The thickness of Bruch’s membrane also increased (p<0.05) by 12 months. By electron microscopy, retinal degeneration and drusen-like structures were observed only in knockout mice. Collectively, our results demonstrate spontaneous degenerative changes in the RPE and the neuroretina of Cd46 -/- mice. These changes resemble those observed in patients with dry-type AMD.
Cd46 -/- mouse develops a phenotype similar to dry-type AMD. It represents a tractable model to facilitate our understanding of AMD.
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