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M.-A. Filion, E. Brown, F. P. Gaillard, Y. Sauve; Impact of Rod Loss on the Retinal Cone Population in the ELOVL4 Mouse Model of Stargardt-Like Dystrophy (STGD3). Invest. Ophthalmol. Vis. Sci. 2010;51(13):4057.
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© ARVO (1962-2015); The Authors (2016-present)
To examine whether the initial loss of rods in STGD3 affects the cone mosaic and opsin expression prior to detectable cone loss
We relied on an ELOVL4 transgenic mouse [line TG1-2, Kuny et al. IOVS (2009), in press] to model STGD3. Firstly, the cone population was quantified on retinal cross sections stained with DAPI and a cone-specific marker (gamma transducin). Secondly, retinas of 12 month old ELOVL4/TG1-2 and wild type (WT) littermates were flatmounted and immunolabeled for M- and S-opsins. Potential differences between groups in M-cone mosaic and M-opsin expression across the retina were estimated using Voronoi domain and fluorescence imaging analysis, respectively.
In WT mice, there is a higher density of photoreceptors in the center than in the periphery. The total number of photoreceptors does not vary with age. In ELOVL4/TG1-2 retinas, there is a progressive loss of photoreceptors beginning by 6 months of age. Near complete photoreceptor loss is achieved at 24 months. At 12 months of age, approximately 50% of the photoreceptors are lost. However, regardless of the area investigated, the cone density remains similar to that found in WTat this time point. The initial photoreceptor loss in transgenic mice is therefore mostly due to rods. Voronoi analysis of the M-cone population further shows no significant variation in mean area and regularity index values between WT and transgenic mice. Finally, the dorso-ventral gradient of M-opsin expression seen in WT is still preserved in ELOVL4/TG1-2 mice. This is in striking contrast with older (24 months) transgenic mice where only sparse, severely distorted cones (confined to a single plane along the outermost periphery of the degenerating retina) can be seen.
Despite an important initial rod loss, the pattern and the phenotype of the M-cones look normal in 12 months old ELOVL4/TG1-2 mice. Studies at later time points will reveal when cones start degenerating.
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