Molecular pathology of age-related macular degeneration

被引：445

作者：

Ding, Xiaoyan ^{[1
,2
]}

Patel, Mrinali ^{[1
,3
]}

Chan, Chi-Chao ^{[1
]}

机构：

[1] NEI, Immunopathol Sect, Immunol Lab, Bethesda, MD 20892 USA

[2] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, Guangzhou 510060, Guangdong, Peoples R China

[3] Howard Hughes Med Inst, Chevy Chase, MD USA

来源：

PROGRESS IN RETINAL AND EYE RESEARCH | 2009年 / 28卷 / 01期

关键词：

Age-related macular degeneration; Inflammation; Single nucleotide polymorphism; Genetics Retinal pigment epithelium; Retinal photoreceptors; Drusen; Vascular endothelial growth factor; Bruch's membrane; Molecular pathology; COMPLEMENT FACTOR-H; RETINAL-PIGMENT EPITHELIUM; APOLIPOPROTEIN-E GENE; CHOROIDAL NEOVASCULAR MEMBRANES; HTRA1 PROMOTER POLYMORPHISM; MITOCHONDRIAL-DNA DAMAGE; GROWTH-FACTOR-BETA; DIETARY-FAT; ANGIOMATOUS PROLIFERATION; STARGARDT-DISEASE;

D O I：

10.1016/j.preteyeres.2008.10.001

中图分类号：

R77 [眼科学];

学科分类号：

100212 ;

摘要：

Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the world. Although the etiology and pathogenesis of AMD remain largely unclear, a complex interaction of genetic and environmental factors is thought to exist. AMD pathology is characterized by degeneration involving the retinal photoreceptors, retinal pigment epithelium, and Bruch's membrane, as well as, in some cases, alterations in choroidal capillaries. Recent research on the genetic and molecular underpinnings of AMD brings to light several basic molecular pathways and pathophysiological processes that might mediate AMD risk, progression, and/or response to therapy. This review summarizes, in detail, the molecular pathological findings in both humans and animal models, including genetic variations in CFH, CX3CR1, and ARMS2/HtrA1, as well as the role of numerous molecules implicated in inflammation, apoptosis, cholesterol trafficking, angiogenesis, and oxidative stress. Published by Elsevier Ltd.

引用

页码：1 / 18

页数：18

共 208 条

[1] A photoreceptor cell-specific ATP-binding transporter gene (ABCR) is mutated in recessive Stargardt macular dystrophy (vol 15, pg 236, 1997) [J].

Allikmets, R .

NATURE GENETICS, 1997, 17 (01) :122-122

[2] Mutation of the Stargardt disease gene (ABCR) in age-related macular degeneration [J].

Allikmets, R ;

Shroyer, NF ;

Singh, N ;

Seddon, JM ;

Lewis, RA ;

Bernstein, PS ;

Peiffer, A ;

Zabriskie, NA ;

Li, YX ;

Hutchinson, A ;

Dean, M ;

Lupski, JR ;

Leppert, M .

SCIENCE, 1997, 277 (5333) :1805-1807

[3] STRUCTURAL AND FUNCTIONAL-ANALYSIS OF THE COMPLEMENT COMPONENT FACTOR-H WITH THE USE OF DIFFERENT ENZYMES AND MONOCLONAL-ANTIBODIES TO FACTOR-H [J].

ALSENZ, J ;

SCHULZ, TF ;

LAMBRIS, JD ;

SIM, RB ;

DIERICH, MP .

BIOCHEMICAL JOURNAL, 1985, 232 (03) :841-850

[4] An animal model of age-related macular degeneration in senescent Ccl-2-or Ccr-2-deficient mice [J].

Ambati, J ;

Anand, A ;

Fernandez, S ;

Sakurai, E ;

Lynn, BC ;

Kuziel, WA ;

Rollins, BJ ;

Ambati, BK .

NATURE MEDICINE, 2003, 9 (11) :1390-1397

[5] Characterization of β amyloid assemblies in drusen:: the deposits associated with aging and age-related macular degeneration [J].

Anderson, DH ;

Talaga, KC ;

Rivest, AJ ;

Barron, E ;

Hageman, GS ;

Johnson, LV .

EXPERIMENTAL EYE RESEARCH, 2004, 78 (02) :243-256

[6] Macrophages inhibit neovascularization in a murine model of age-related macular degeneration [J].

Apte, Rajendra S. ;

Richter, Jennifer ;

Herndon, John ;

Ferguson, Thomas A. .

PLOS MEDICINE, 2006, 3 (08) :1371-1381

[7] TLR4 mutations are associated with endotoxin hyporesponsiveness in humans [J].

Arbour, NC ;

Lorenz, E ;

Schutte, BC ;

Zabner, J ;

Kline, JN ;

Jones, M ;

Frees, K ;

Watt, JL ;

Schwartz, DA .

NATURE GENETICS, 2000, 25 (02) :187-+

[8] The photoreceptor rim protein is an ABC transporter encoded by the gene for recessive Stargardt's disease (ABCR) [J].

Azarian, SM ;

Travis, GH .

FEBS LETTERS, 1997, 409 (02) :247-252

[9] Gene-environment interaction in progression of AMD:: the CFH gene, smoking and exposure to chronic infection [J].

Baird, Paul N. ;

Robman, Luba D. ;

Richardson, Andrea J. ;

Dimitrov, Peter N. ;

Tikellis, Gabriella ;

McCarty, Catherine A. ;

Guymer, Robyn H. .

HUMAN MOLECULAR GENETICS, 2008, 17 (09) :1299-1305

[10] Apolipoprotein (APOE) gene is associated with progression of age-related macular degeneration (AMD) [J].

Baird, PN ;

Richardson, AJ ;

Robman, LD ;

Dimitrov, PN ;

Tikellis, G ;

McCarty, CA ;

Guymer, RH .

HUMAN MUTATION, 2006, 27 (04) :337-342

← 1 2 3 4 5 6 7 8 9 10 →