Comparison of drusen and modifying genes in autosomal dominant radial drusen and age-related macular degeneration

• Published in: Retina (Philadelphia, Pa.) Vol. 35; no. 1; p. 48
• Main Authors: Sohn, Elliott H, Wang, Kai, Thompson, Stewart, Riker, Megan J, Hoffmann, Jeremy M, Stone, Edwin M, Mullins, Robert F
• Format: Journal Article
• Language: English
• Published: United States 01.01.2015
• Subjects: Adult; Aged; Aged, 80 and over; Alleles; Collagen Type IV - metabolism; Complement Factor H - genetics; Corneal Dystrophies, Hereditary - genetics; Corneal Dystrophies, Hereditary - metabolism; Corneal Dystrophies, Hereditary - pathology; Extracellular Matrix Proteins - genetics; Extracellular Matrix Proteins - metabolism; Female; Genotyping Techniques; High-Temperature Requirement A Serine Peptidase 1; Humans; Male; Middle Aged; Optic Disk Drusen - congenital; Polymorphism, Single Nucleotide; Proteins - genetics; Retinal Drusen - genetics; Retinal Drusen - metabolism; Retinal Drusen - pathology; Serine Endopeptidases - genetics; Serum Amyloid P-Component - metabolism; Tissue Donors; Vitronectin - metabolism; Wet Macular Degeneration - genetics; Wet Macular Degeneration - metabolism; Wet Macular Degeneration - pathology; Young Adult
• ISSN: 1539-2864
• DOI: 10.1097/IAE.0000000000000263

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. 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. 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. 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.