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I. A. Bhutto, T. Baba, C. Merges, D. S. McLeod, M. K. Mathews, G. A. Lutty; Lipoprotein A and C-Reactive Protein in Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4936.
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Atherosclerosis, a multifactorial disease driven by inflammatory reactions, has long been postulated to be associated with age-related macular degeneration (AMD). Lipoprotein (a) or Lp(a) binds to LDL and is an atherogenic lipoprotein. C-reactive protein (CRP) is an acute phase protein, which actively contributes to inflammatory processes and has been found to colocalize with oxidized LDL (oxLDL) at the level of the artery wall. Thus, elevated levels of lipoproteins and CRP are linked to premature development of atherosclerotic lesion. In this study, we examined the localization of Lp(a) and CRP in aged control human retina and choroid and compared it with localization and relative levels in AMD eyes.
Alkaline phosphatase immunohistochemistry was performed using polyclonal antibodies against Lp(a) and CRP on cryopreserved sections from macular areas of aged control donor eyes (n=13; mean age 79 yrs) and eyes with AMD (n=20; mean age 83 yrs). CD34 antibody was used as a marker for vascular endothelial cells. Three independent masked observers scored the reaction product (0-8). Mean scores from the control and AMD eyes were analyzed using 1-way analysis of variance and unpaired Student t-test.
In aged control eyes, the choriocapillaris (CC) and intercapillary pillars (ICP) had the most prominent immunostaining for Lp(a) and CRP. Moderate immunoreactivity of both antibodies was also present in retinal and large choroidal blood vessels. In AMD eyes, the immunoreactivity of CRP was significantly higher in retinal vessels compared to the control eyes. A significant elevation of Lp(a) was observed in choroidal arteries in AMD. In retinal pigment epithelium-Bruch’s membrane-CC complex including ICP and choroidal stroma, the immunoreactivity of CRP was also significantly higher than in controls. Drusen and basal laminar deposits were intensively positive for Lp(a) and CRP.
These immunohistochemical findings demonstrate that Lp(a) and CRP are associated with blood vessels of retina and choroid. The higher levels of Lp(a) and CRP expression in AMD choroid may represent a possible atherogenic risk factor and suggest that increased Lp(a) and CRP may be contributing to AMD pathogenesis.
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