COMPARISON OF DRUSEN AND MODIFYING GENES IN AUTOSOMAL DOMINANT RADIAL DRUSEN AND AGE-RELATED MACULAR DEGENERATION

被引:26
作者
Sohn, Elliott H. [1 ,2 ]
Wang, Kai [1 ,3 ]
Thompson, Stewart [1 ,2 ]
Riker, Megan J. [1 ,2 ]
Hoffmann, Jeremy M. [1 ,2 ]
Stone, Edwin M. [1 ,2 ,4 ]
Mullins, Robert F. [1 ,2 ]
机构
[1] Univ Iowa, Stephen A Wynn Inst Vis Res, Iowa City, IA 52242 USA
[2] Univ Iowa, Dept Ophthalmol & Visual Sci, Iowa City, IA 52242 USA
[3] Univ Iowa, Dept Biostat, Iowa City, IA 52242 USA
[4] Univ Iowa, Howard Hughes Med Inst, Iowa City, IA 52242 USA
来源
RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES | 2015年 / 35卷 / 01期
基金
美国国家卫生研究院;
关键词
age-related macular degeneration; ARMS2; autosomal dominant radial drusen; CFH; drusen; extracellular matrix; genetics; histology; modifying genes; COMPLEMENT FACTOR-H; EXTRACELLULAR-MATRIX; ABERRANT ACCUMULATION; MALATTIA LEVENTINESE; TISSUE INHIBITOR; MUTATIONS; EFEMP1; ARMS2; RISK; POLYMORPHISM;
D O I
10.1097/IAE.0000000000000263
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
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.
引用
收藏
页码:48 / 57
页数:10
相关论文
共 39 条
[1]   Perspective - A role for local inflammation in the formation of drusen in the aging eye [J].
Anderson, DH ;
Mullins, RF ;
Hageman, GS ;
Johnson, LV .
AMERICAN JOURNAL OF OPHTHALMOLOGY, 2002, 134 (03) :411-431
[2]   IMPROVED METHOD FOR OBTAINING 3-MU-M CRYOSECTIONS FOR IMMUNOCYTOCHEMISTRY [J].
BARTHEL, LK ;
RAYMOND, PA .
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 1990, 38 (09) :1383-1388
[3]   Mutations in ABCC6 cause pseudoxanthoma elasticum [J].
Bergen, AAB ;
Plomp, AS ;
Schuurman, EJ ;
Terry, S ;
Breuning, M ;
Dauwerse, H ;
Swart, J ;
Kool, M ;
van Soest, S ;
Baas, F ;
ten Brink, JB ;
de Jong, PTVM .
NATURE GENETICS, 2000, 25 (02) :228-231
[4]   AN INTERNATIONAL CLASSIFICATION AND GRADING SYSTEM FOR AGE-RELATED MACULOPATHY AND AGE-RELATED MACULAR DEGENERATION [J].
BIRD, AEC ;
BRESSLER, NM ;
BRESSLER, SB ;
CHISHOLM, IH ;
COSCAS, G ;
DAVIS, MD ;
DEJONG, PTVM ;
KLAVER, CCW ;
KLEIN, BEK ;
KLEIN, R ;
MITCHELL, P ;
SARKS, JP ;
SARKS, SH ;
SOURBANE, G ;
TAYLOR, HR ;
VINGERLING, JR .
SURVEY OF OPHTHALMOLOGY, 1995, 39 (05) :367-374
[5]  
CAMPOCHIARO PA, 1986, INVEST OPHTH VIS SCI, V27, P1615
[6]   Distribution of the collagen IV isoforms in human Bruch's membrane [J].
Chen, L ;
Miyamura, N ;
Ninomiya, Y ;
Handa, JT .
BRITISH JOURNAL OF OPHTHALMOLOGY, 2003, 87 (02) :212-215
[7]  
Curcio C.A., 2012, Structure, Function and Pathology of Bruch's Membrane, Vfifth
[8]   Complement factor H polymorphism and age-related macular degeneration [J].
Edwards, AO ;
Ritter, R ;
Abel, KJ ;
Manning, A ;
Panhuysen, C ;
Farrer, LA .
SCIENCE, 2005, 308 (5720) :421-424
[9]   Retinal findings in patients with Alport Syndrome: expanding the clinical spectrum [J].
Fawzi, A. A. ;
Lee, N. G. ;
Eliott, D. ;
Song, J. ;
Stewart, J. M. .
BRITISH JOURNAL OF OPHTHALMOLOGY, 2009, 93 (12) :1606-1611
[10]   Mouse genetics and proteomic analyses demonstrate a critical role for complement in a model of DHRD/ML, an inherited macular degeneration [J].
Garland, Donita L. ;
Fernandez-Godino, Rosario ;
Kaur, Inderjeet ;
Speicher, Kaye D. ;
Harnly, James M. ;
Lambris, John D. ;
Speicher, David W. ;
Pierce, Eric A. .
HUMAN MOLECULAR GENETICS, 2014, 23 (01) :52-68