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

Elliott H Sohn; Kai Wang; Stewart Thompson; Megan J Riker; Jeremy M Hoffmann; Edwin M Stone; Robert F Mullins

doi:10.1097/IAE.0000000000000263

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

Journal article

Open access

Peer reviewed

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

Elliott H Sohn, Kai Wang, Stewart Thompson, Megan J Riker, Jeremy M Hoffmann, Edwin M Stone and Robert F Mullins

Retina (Philadelphia, Pa.), Vol.35(1), pp.48-57

01/2015

DOI: 10.1097/IAE.0000000000000263

PMCID: PMC5513174

PMID: 25077532

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Abstract

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.

Retinal Drusen - genetics

Retinal Drusen - metabolism

Humans

Middle Aged

Corneal Dystrophies, Hereditary - genetics

Male

Wet Macular Degeneration - genetics

Genotyping Techniques

Young Adult

Corneal Dystrophies, Hereditary - pathology

Wet Macular Degeneration - metabolism

Serine Endopeptidases - genetics

Aged, 80 and over

Adult

Female

Extracellular Matrix Proteins - metabolism

Collagen Type IV - metabolism

Retinal Drusen - pathology

Wet Macular Degeneration - pathology

Extracellular Matrix Proteins - genetics

High-Temperature Requirement A Serine Peptidase 1

Corneal Dystrophies, Hereditary - metabolism

Vitronectin - metabolism

Proteins - genetics

Optic Disk Drusen - congenital

Alleles

Aged

Polymorphism, Single Nucleotide

Serum Amyloid P-Component - metabolism

Tissue Donors

Complement Factor H - genetics

Details

Title: Subtitle: Comparison of drusen and modifying genes in autosomal dominant radial drusen and age-related macular degeneration
Creators: Elliott H Sohn - University of Iowa, The University of Iowa Institute for Vision Research
Kai Wang - University of Iowa, Biostatistics
Stewart Thompson
Megan J Riker - University of Iowa, The University of Iowa Institute for Vision Research
Jeremy M Hoffmann - University of Iowa, The University of Iowa Institute for Vision Research
Edwin M Stone - University of Iowa, Ophthalmology and Visual Sciences
Robert F Mullins - University of Iowa, The University of Iowa Institute for Vision Research
Resource Type: Journal article
Publication Details: Retina (Philadelphia, Pa.), Vol.35(1), pp.48-57
DOI: 10.1097/IAE.0000000000000263
PMID: 25077532
PMCID: PMC5513174
NLM abbreviation: Retina
ISSN: 1539-2864
eISSN: 1539-2864
Publisher: United States
Grant note: EY017451 / NEI NIH HHS R01 EY017451 / NEI NIH HHS R01 EY016822 / NEI NIH HHS EY016822 / NEI NIH HHS Howard Hughes Medical Institute
Language: English
Date published: 01/2015
Academic Unit: Iowa Neuroscience Institute; Biostatistics; Ophthalmology and Visual Sciences
Record Identifier: 9983979980702771

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