Posted on Jan 08, 2010, 6 a.m.
UK researchers discover that blood protein Factor H and C-reactive protein interplay at the molecular level in Age-Related Macular Degeneration (AMD).
Age-related macular degeneration (AMD) is an eye disease that affects the macula, the part of the retina that allows one to see fine detail. The leading cause of age-related vision loss today, there is no known cure for AMD but existing therapies aim to treat the symptoms and delay progression. In that the earliest hallmark of AMD is the appearance of “drusen,” which are protein, lipid and zinc deposits under the retinal pigment epithelial cells, Azubuike I. Okemefuna, from University College London (United Kingdom), and colleagues studied two proteins involved in drusen formation -- blood protein Factor H and C-reactive protein (CRP). In that Factor H binds to C-reactive protein when C-reactive protein is present in large amounts, as in the case of infection, to reduce the potentially damaging effects of an overactive immune system., the researchers found that in the aging eye, low level of C-reactive protein activity will enable the normal processes of clearance of dead cells at the retina through mild inflammation. As a result of this condition of high inflammation, the levels of C-reactive protein in the retina will increase dramatically, and uncontrolled C-reactive protein activity causes damage to the retina, which is followed by more inflammation and then even more damage to the retina, and so on, causing the drusen deposits. The team also found that a genetically different form of Factor H does not bind to the C-reactive protein quite as well as the normal one, making people who carry the modified protein more vulnerable to an immune system attack in the eye and, thus, drusen buildup. The researchers explain that: "In normal individuals, further damage to the retina by prolonged exposure to high levels of C-reactive protein is prevented by Factor H. C-reactive protein also prevents Factor H from clumping together and initiating the processes that lead to drusen formation. Both these 'good' activities of Factor H are much reduced in the genetically different form of Factor H."
Azubuike I. Okemefuna, Lasse Stach, Sudeep Rana, Akim J. Ziai Buetas, Jayesh Gor, Stephen J. Perkins. “C-reactive Protein Exists in an NaCl Concentration-dependent Pentamer-Decamer Equilibrium in Physiological Buffer.” J. Biol. Chem. 2010 285: 1041-1052. First Published on November 10, 2009, doi:10.1074/jbc.M109.044495.