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M. Waugh, K. A. Vessey, M. M. Ward, E. L. Fletcher; Retinal Function is Not Affected in the MCP-1null Mouse Model of Age Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2010;51(13):6143.
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Dysfunction in chemokine signaling has been implicated in development of Age Related Macular Degeneration (AMD). MCP-1 null mice are known to exhibit many of the signs of AMD and have been suggested as a possible animal model. The aim of this study was to characterize changes in retinal function and dark adaptation in control and MCP-1null mice with age and to correlate this with the development of pathological signs of AMD.
Retinal function was analysed in MCP-1null (N=11-18) and C57Bl6 (N=10-15) from 3 to 15 months of age using the electroretinogram (ERG) using a twin flash paradigm over a range of light intensities. In addition, dark adaptation was investigated by measuring photoreceptor recovery following pigment bleaching. The retinal fundus from control and MCP1-1null mice 3, 12 or 15 months of age was examined and eyes removed and aldehyde fixed for histological analysis.
Drusen-like deposits were observed in mice 15 months of age. Functional changes were noted in both control and MCP-1null mice with age (P<0.01). In particular, there was a loss in the amplitude of the a-wave between 3 and 15 months. However, photoreceptoral dysfunction was similar in both control and MCP-1 null mice (15 months: C57Bl6-265+26µV; MCP-206+41µV). There was no difference in photoreceptor sensitivity at any ages examined. A loss in post-receptoral function was evaluated by examining the amplitude of the b-wave with age. Similar to the photoreceptor findings, a loss of the b-wave was noted with age, but there was no difference between control and MCP-1 null mice. The affect of age and mouse strain on inner versus outer retinal function was evaluated by comparing the relative loss of the a-wave to b-wave in the different cohorts of mice. The loss of retinal function with age is predominantly explained by a loss in photoreceptor function.
Although ageing was associated with a significant reduction in photoreceptoral function, there was no difference in MCP-1 null mice despite obvious ocular fundus differences. These data suggest that retinal fundus changes do not affect a large enough proportion of photoreceptors in MCP-1 null mice to elicit a functional change over and above that from ageing.
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