Altered Retinal Pigment Epithelium Morphology Is Associated With Decreased Expression of Complement Regulatory Protein CD46 and Ion Transporter MCT3 in Geographic Atrophy of Age-Related Maculopathy

Abstract

Purpose: : To evaluate zones across geographic atrophy (GA) lesions for differences in location and intensity of 2 proteins-- membrane cofactor protein (CD46), a complement regulator, and MCT3, an ion transporter-- both of which are present in the basolateral membrane of normal retinal pigment epithelium (RPE).

Methods: : From donors of known CFH genotype, macular tissue from 10 eyes with GA, and without other chorioretinal pathology, and 5 age-matched control eyes were fixed in 4% paraformaldehyde and cryosectioned at 10 µm. CD46 and MCT3 were stained using alkaline phosphatase-based immunohistochemistry in sections selected from 3 planes across GA lesions and at comparable locations in normal controls. Staining characteristics were graded for both proteins within zones of RPE morphology based on the ALARMGS system. Statistical analysis was performed using the Chi square test.

Results: : Grading results of CD46 and MCT3 staining associated with RPE are shown in Table 1.

Conclusions: : The staining intensity and basolateral localization of both CD46 and MCT3 diminishes with the progression of RPE alteration across GA lesions. Strikingly, changes in protein staining characteristics are apparent even in RPE grades associated with little or no atrophy indicating that alterations in the distribution of these proteins occur in the earliest stages of GA. Furthermore the early loss of polarity indicated by our findings may have wide implications for other important RPE functions.

Keywords: age-related macular degeneration • retinal pigment epithelium • retinal degenerations: cell biology