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Michael J Landowski, Una L Kelly, Marybeth Groelle, Jindong Ding, Catherine Bowes Rickman; Exogenous CFH Contributes to Complement Regulation in the Eyes of Cfh-Deficient Animals.. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1321. doi: https://doi.org/.
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Complement factor H (CFH) has been implicated as a susceptibility gene for age-related macular degeneration (AMD). CFH is an inhibitor of complement activation that accelerates the decay of the C3 convertase and acts as a cofactor for factor I-mediated inactivation of C3b. CFH is predominantly produced and secreted by the liver into the circulation. However, CFH is also produced locally in the eye by cells such as the retinal pigment epithelium. It is currently unknown how and what extent CFH from the circulation can infiltrate the choriocapillaris and Bruch’s membrane to contribute to the pool of CFH in the posterior eye. We investigated the extent of the contribution of CFH from the circulation to complement regulation in the posterior eye by exogenously introducing purified CFH into Cfh-deficient mice.
Purified mouse and human CFH (YY402 and HH402) was IP injected into Cfh-deficient animals. These animals were sacrificed and perfused at 24 and 72 hours post-injection. To assess the localization and functionality of exogenously-added CFH in these animals, eyes and sera were collected and analyzed using Western blot analysis and immunohistochemistry for CFH, C3, and Factor B (FB). As a control, age-matched Cfh-deficient animals were injected with an equal volume of phosphate saline buffer (PBS).
We detected CFH in the posterior eye by immunohistochemistry and Western blot analysis. This CFH was functional as measured by C3 and FB levels in the plasma and eye lysates by Western blot analysis. We have also compared the biochemical efficiencies of murine and human CFH in regulating complement in the murine eye.
The pool of CFH in the posterior eye originates from local and systemic sources, suggesting that the posterior eye depends on both sources of CFH for its regulation of complement activation.
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