June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Histological Correlation of Basement Membrane Deposits in Age-Related Macular Degeneration and Renal Dense Deposit Disease
Author Affiliations & Notes
  • Lauren Malaya
    The University of Texas Medical Branch at Galveston School of Medicine, Galveston, Texas, United States
  • Marjan Afrouzian
    The University of Texas Medical Branch at Galveston, Galveston, Texas, United States
  • Praveena Gupta
    The University of Texas Medical Branch at Galveston, Galveston, Texas, United States
  • Footnotes
    Commercial Relationships   Lauren Malaya, None; Marjan Afrouzian, None; Praveena Gupta, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 270. doi:
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      Lauren Malaya, Marjan Afrouzian, Praveena Gupta; Histological Correlation of Basement Membrane Deposits in Age-Related Macular Degeneration and Renal Dense Deposit Disease. Invest. Ophthalmol. Vis. Sci. 2021;62(8):270.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : The pathophysiology of drusen formation in dry age-related macular degeneration (AMD) is incompletely understood. Studies have found common molecular components of the complement system in drusen of dry AMD and dense deposit disease (DDD) of the kidney. To understand the pathophysiology of AMD we compared the morphological features of the two diseases by light (LM) and immunofluorescence (IF) microscopy.

Methods : Human donor eyes with dry AMD (n=3) and kidney biopsies from patients diagnosed with DDD (n=2) were studied in compliance with the institutional guidelines. Formalin-fixed and snap-frozen fresh samples from both eye and kidney specimens were cut at 2 and 5 microns, respectively, and stained with H&E, PAS, Masson’s trichrome, Jones silver, Verhoeff’s stains, and anti-C3 antibody. Unstained sections were used as controls for autofluorescence. Slides were analyzed under bright field and confocal fluorescence microscope.

Results : Morphological similarities were observed between drusen and DDD deposits: Significant thickening of the Bruch’s membrane (BrM) and glomerular basement membrane (GBM) was found in both diseases by PAS stain, suggesting the presence of excess matrix formation composed of polysaccharides and mucins. While multiple large laminar deposits of drusen were diffusely dispersed alongside the BrM, by LM, the GBM in DDD did not reveal the deposits by LM. By PAS stain, the cleavage edge – splitting of BrM between the basement membrane of the RPE and the inner collagenous layer – was observed in AMD specimens, while the DDD specimens revealed double contouring of the GBM. Abundant notched inter-capillary pillars were seen in AMD, mirroring increases in mesangial matrix seen in DDD specimens. Jones silver staining revealed extracellular matrix (abundance of oxidized carbohydrates), particularly around capillaries in both specimens. By IF, linear deposits of C3 were found in dry AMD along the BrM compared to strong deposits of C3 seen along the GBM in DDD sections.

Conclusions : We show similarities in the structural defects in the membranes of dry AMD eye and the DDD kidney. Moreover, C3 deposition in the BrM and GBM in drusen and DDD have similarities in terms of pattern and intensity. As DDD has a complement-mediated pathogenesis, hypothetically, it is possible that the pathogenesis in AMD is also related to complement system dysfunction.

This is a 2021 ARVO Annual Meeting abstract.

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