Abstract
Purpose::
Age-related macular degeneration (AMD) is a complex disease. Oxidative injury and chronic inflammation have been implicated in its pathogenesis and elevated serum or choroidal CRP appears to be associated with an increased risk. Therefore, the following study was performed to examine the role of CRP and oxidant injury as causative factors for AMD development in mice.
Methods::
12 month old male C57/BL6 mice expressing the human CRP gene (CRPtg) were fed a standard high fat diet (Bioserve- F5200) containing 0.05% hydroquinone (HQ) for six months. Age matched control mice were fed regular rodent chow. Blood samples were collected prior to feeding the diet and at the end of 6 months. Serum human CRP levels were measured by ELISA. Enucleated mouse eyes were processed for light and transmission electron microscopy (TEM).
Results::
CRPtg mice maintained a serum CRP level of 5.9 µg/ml (n=3). Feeding HQ/high fat diet did not appreciably boost CRP expression above its basal level (< twofold, n=2). After six months on the HQ/high fat diet, mice weighed 37.3± 1.5 g (n=3) compared to 29.7 ±1.4 g (n=3) on the standard rodent fed control diet. For eyes from HQ/high fat fed CRPtg, TEM revealed disruption or absence of basal infoldings of the retinal pigment epithelium (RPE). The elastic layer of Bruch's membrane (BrM) was irregular. There were electron dense material and fragmented membranous material consistent with basal laminar deposits of thickness varying between 1 - 4 µm accumulated between the RPE and BrM. Neither CRPtg mice fed a normal diet nor control (not CRP transgenic) mice fed the HQ/high fat diet demonstrated similar abnormal ultrastructure.
Conclusions::
Sub-RPE deposits and other pathological changes akin to early AMD occur in eyes of mice with known AMD risk factors. Our findings implicate that chronic inflammation in general and CRP per se is permissive for development of AMD after repetitive oxidant injury.
Keywords: age-related macular degeneration • retinal pigment epithelium • inflammation