Journal
RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
Volume 35, Issue 1, Pages 48-57Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/IAE.0000000000000263
Keywords
age-related macular degeneration; ARMS2; autosomal dominant radial drusen; CFH; drusen; extracellular matrix; genetics; histology; modifying genes
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Funding
- National Institutes of Health [EY017451, EY016822]
- Howard Hughes Medical Institute
- Hansjoerg E.J.W. Kolder Professorship for Best Disease Research
- NATIONAL EYE INSTITUTE [R01EY016822, R01EY017451] Funding Source: NIH RePORTER
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Background: Autosomal dominant radial drusen (ADRD), also termed Malattia Leventinese and Doyne honeycomb retinal dystrophy, causes early-onset vision loss because of mutation in EFEMP1. Drusen in an exceedingly rare ADRD human donor eye was compared with eyes affected with age-related macular degeneration (AMD). This study also elucidated whether variations in high-risk AMD genotypes modify phenotypic severity of ADRD. Methods: Morphologic and histochemical analyses of drusen in one ADRD donor and seven AMD donors. Evaluation of complement factor H (CFH) and ARMS2/HTRA1 alleles in a cohort of 25 subjects with ADRD. Results: Autosomal dominant radial drusen had unique onion skin-like lamination but otherwise shared many compositional features with hard, nodular drusen and/or diffuse soft drusen with basal deposits. Autosomal dominant radial drusen also possessed collagen type IV, an extracellular matrix protein that is absent in age-related drusen. Antibodies directed against the membrane attack complex showed robust labeling of ADRD. Vitronectin and amyloid P were present in drusen of both types. High-risk alleles in the CFH and ARMS2/HTRA1 genes were not associated with increasing ADRD severity. Conclusion: Drusen from ADRD and AMD exhibit overlap of some major constituents, but ADRD exhibit distinct alterations in the extracellular matrix that are absent in AMD.
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