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S. D. Vogt, C. A. Curcio, N. E. Medeiros, J. A. Kimble, R. W. Read; Complement Regulatory Protein CD46: Altered Distribution on the Retinal Pigment Epithelium (RPE) in Age-Related Macular Degeneration (ARMD). Invest. Ophthalmol. Vis. Sci. 2007;48(13):3013.
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To determine if variations in RPE morphology in geographic atrophy (GA) due to ARMD are associated with variations in location or intensity of the complement regulator CD46, a constitutive basolateral surface protein of the RPE.
Four human donor eyes with GA and without other gross ocular pathology and one age-matched control eye were preserved in buffered 4% paraformaldehyde. Macular blocks of tissue were cryosectioned at 10 µm. Three planes of sections across each GA lesion were analyzed, each including at least one transitional zone. For the normal eye, one plane through the central macula was sectioned. CD46 staining was carried out using alkaline phosphatase-based immunohistochemistry. CD46 staining was graded for zones of defined RPE morphology and tabulated for multiple occurrences of each RPE grade (Table 1). Data were analyzed using the Chi square test.
Table 1 details the number of zones having the indicated RPE grade and CD46 staining characteristics. A statistically difference in both CD46 staining characteristics was seen across the various RPE grades.
CD46 staining is less intense and less well localized to the basolateral portion of RPE cells in areas of more pronounced GA. This suggests that loss of the normal pattern of CD46 staining may be functionally significant for the RPE bordering GA lesions, even for cells with minimally altered morphology (grade 1). CD46 is a regulator of complement activation and evidence of complement's role in ARMD exists. Whether the alterations in CD46 seen on the RPE of GA lesions are a cause or effect of the pathophysiology of geographic atrophy requires additional study. Subsequent analyses will compare these results to Bruch’s membrane health and RPE polarity status as revealed by other markers.
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