Dry Age-Related Macular Degeneration and Dense Deposit Disease: A Histopathological Comparison of Macular and Renal Lesions

TL;DR

This study compares the eye disease dry AMD and kidney disease DDD, finding similar tissue changes and complement protein deposits, suggesting a shared underlying cause.

Contribution

The study reveals morphological and complement-related similarities between dry AMD and DDD, suggesting a potential common pathogenesis.

Findings

Dry AMD and DDD both show basement membrane thickening and C3b deposits.

Drusen in AMD and glomerular basement membrane changes in DDD share similar pathological features.

C3b is present in both macular drusen and glomerular basement membranes in the two diseases.

Abstract

Background

Dry age-related macular degeneration (AMD) and dense deposit disease (DDD) in the kidney have molecular commonality due to the involvement of the complement system. DDD is a renal disease linked to defects of the complement alternative pathway, and in dry AMD, complement components have been found within drusen. In this study, pathologic features of dry AMD and DDD were studied by light and immunofluorescence microscopy to clarify whether morphologic similarities exist between the two diseases.

Methodology

Sections were obtained from (1) the macula of four patients with dry AMD; (2) renal biopsies of two DDD patients; (3) the macula from healthy eye donors; and (4) a kidney biopsy of a normal human subject. Sections were stained with hematoxylin and eosin, periodic acid-Schiff (PAS), and periodic-acid-methenamine silver for light microscopy and with C3b antisera for fluorescence microscopy.

Results

Changes observed in dry AMD specimens included (1) the presence of numerous drusen containing PAS- and silver-positive material; (2) thickening of the Bruch’s membrane; (3) thickening of prominent PAS-positive intercapillary pillars; and (4) degeneration and dropouts in the choriocapillaris and dilatation and congestion of vessels in the Sattler’s layer. In comparison, changes in the DDD specimens included (1) thickening of the glomerular basement membrane (GBM) and presence of double contours; and (2) mesangial and endocapillary proliferation. C3b was positive in both macular drusen and along the GBM.

Conclusions

Basement membrane changes in dry AMD share morphological similarities with the GBM changes in DDD, and, in both diseases, C3b is deposited, suggesting that the association between the two diseases possibly reflects a common pathogenesis.

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