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Jindong Ding, Una Kelly, Marybeth Groelle, Catherine Bowes Rickman; Human Complement Factor H (CFH) Transgene Expression Rescues the Visual Function and Retina Abnormalities in Aged cfh-/- Mice. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5015.
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Complement factor H (CFH) polymorphisms are the strongest genetic risk factors associated with age-related macular degeneration. We have previously generated bacterial artificial chromosome (BAC) transgenic mouse lines expressing the human Y402 or H402 CFH variants. We have also shown that human CFH protein can replace mouse cfh in the mouse complement alternative pathway when crossed to the cfh-/- mice (CFH-Tg,cfh-/-). In the present work, we evaluated the ocular phenotype of the CFH-Tg,cfh-/- mice. Specifically, we examined whether the retinal degeneration in the cfh-/- mice can be rescued by the human CFH protein.
Experiments were performed on two-year-old cfh-/-, CFH-Tg,cfh-/- and C57 mice. The retina visual function was measured by electroretinogram (ERG). Eyes were fixed and embedded in resin. Semi-thin sections were examined to evaluate the gross morphology of the retina. Approximately 60 transmission electron microscopic images per retina were taken at regular intervals across the superior-inferior plane to measure the thickness of sub-RPE deposit.
The b-wave amplitude of the ERG was significantly reduced in the cfh-/- mice, compared to the C57 mice. The b-wave amplitude of the CFH-Tg,cfh-/- mice was partially recovered. Initial evaluation did not detect any differences in the gross retina structure. Contrary to previous studies, we found that aged cfh-/- mice have considerably more sub-RPE deposit than age-matched C57 mice. However, the thickness of these basal deposits were reduced in the CFH-Tg,cfh-/- mice.
Human CFH protein can partially rescue the retinal ERG deficit and reduce the amount of sub-RPE basal deposit caused by cfh gene deletion.
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