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Maria Hernandez, Laura Garcia-Garcia, Sergio Recalde, Patricia Fernandez, Maite Moreno-Orduña, Laura Fernandez Sanchez, Laura Ramirez, Pedro de la Villa, Nicolas Cuenca, Alfredo Garcia-Layana; MOLECULAR AND FUNCTIONAL CHANGES IN THE RETINA OF MICE DEFICIENT IN COMPLEMENT FACTOR H AND APOLIPOPROTEIN E. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3462.
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© ARVO (1962-2015); The Authors (2016-present)
The Apolipoprotein E deficient mouse (apoE-/-), an experimental model of genetic hypercholesterolemia, shows some retinal alterations. Complement factor H (cfh) is involved in inflammatory processes associated with retinal degeneration such as Age-related Macular Degeneration (AMD). We aimed to investigate the effect of the absence of CFH and apoE genes in the expression of specific molecular markers and to study the electrophysiological activity in mouse retinas.
Twelve-month old wild type (WT), cfh-/-/apoE-/- (DKO) and cfh+/-/apoE-/- (EKHH) mice were divided into 3-5 animals per group. Electroretinograms (ERGs) were measured, the a-wave was used as an index of outer retinal function, whereas the b-wave, oscillatory potentials (OPs) and scotopic threshold response (STR) were used as indices of inner retinal function. The animals were euthanatized and enucleated. Retinal pigment epithelium (RPE) were subjected to immunofluorescence using Zonula ocludens-1 (ZO-1) antibody. Cryostat sections of the other eye were immunostaining to detect outer and inner plexiform layer (OPL, IPL) (synaptophysin, bassoon), horizontal cells (PKC, Calbindin) and inflammation-related molecules (active caspase-1 and C5b9). Photographs were taken by confocal microscopy.
ZO-1 flat mount images showed alterations of intercellular junctions between epithelial cells in the EKHH and DKO vs. WT mice. The number of rows of photoreceptor nuclei were similar in EKHH and WT retinas, although we observed in DKO a reduction of the thickness in the outer nuclear layer. The dendrites of the horizontal cells in EKHH retinas were numerous. Moreover, presence of caspase-1 positive cells and C5b9 immunoreactivity were observed in the ONL and INL in EKHH retinas. ERG recordings from DKO mice showed their a-, b-wave and STR amplitudes were reduced when compared to WT. There was no significant changes in the ERGs of the EKHH mice.
ApoE and cfh genes seem to be related to the maintenance of RPE cytoarchitecture. Moreover, they could be involved in direct and indirect contact of photoreceptors with some retinal cells. The morphological changes in DKO mice, correspond to alteratios in functional retina. In addition, some inflammatory pathways could be active in transgenic mice lacking apoE and cfh.
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