Abstract

The proposed research is focused on the origin and composition of drusen and the pathogenesis of AMD. Preliminary studies have identified specific drusen-associated molecules (DRAMs), many of which are circulating plasma proteins and known participants in the process of fibrinolysis, thrombosis, inflammation, and/or the immune response. The emphasis of the proposal is on determining how normal and abnormal plasma proteins or the autoimmune response may be involved in the formation of drusen. To this end, four specific aims are designed to determine: (1) whether molecular abnormalities in drusen-associated plasma proteins are associated with the incidence of drusen and AMD; (2) whether specific molecular isoforms and/or abnormal concentrations of plasma proteins are associated with the incidence of drusen and AMD; (3) the nature of the autoimmune response associated with drusen and AMD; and (4) the effects of DRAMs on in vitro cell cultures. This proposal is related to two others through their common attempt to define a relationship between drusen, choroidal abnormalities and AMD.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY011527-02
Application #
2459187
Study Section
Special Emphasis Panel (ZRG1-VISC (01))
Project Start
1996-08-01
Project End
1999-07-31
Budget Start
1997-08-01
Budget End
1998-07-31
Support Year
2
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
University of California Santa Barbara
Department
Type
Organized Research Units
DUNS #
City
Santa Barbara
State
CA
Country
United States
Zip Code
93106

  Publications

Isas, J Mario; Luibl, Volker; Johnson, Lincoln V et al. (2010) Soluble and mature amyloid fibrils in drusen deposits. Invest Ophthalmol Vis Sci 51:1304-10
Kochounian, Harold; Johnson, Lincoln V; Fong, Henry K W (2009) Accumulation of extracellular RGR-d in Bruch's membrane and close association with drusen at intercapillary regions. Exp Eye Res 88:1129-36
Radeke, Monte J; Peterson, Katie E; Johnson, Lincoln V et al. (2007) Disease susceptibility of the human macula: differential gene transcription in the retinal pigmented epithelium/choroid. Exp Eye Res 85:366-80
Hageman, Gregory S; Hancox, Lisa S; Taiber, Andrew J et al. (2006) Extended haplotypes in the complement factor H (CFH) and CFH-related (CFHR) family of genes protect against age-related macular degeneration: characterization, ethnic distribution and evolutionary implications. Ann Med 38:592-604
Johnson, P T; Betts, K E; Radeke, M J et al. (2006) Individuals homozygous for the age-related macular degeneration risk-conferring variant of complement factor H have elevated levels of CRP in the choroid. Proc Natl Acad Sci U S A 103:17456-61
Gehrs, Karen M; Anderson, Don H; Johnson, Lincoln V et al. (2006) Age-related macular degeneration--emerging pathogenetic and therapeutic concepts. Ann Med 38:450-71
Hageman, Gregory S; Anderson, Don H; Johnson, Lincoln V et al. (2005) A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration. Proc Natl Acad Sci U S A 102:7227-32
Johnson, Patrick T; Brown, Meghan N; Pulliam, Bryce C et al. (2005) Synaptic pathology, altered gene expression, and degeneration in photoreceptors impacted by drusen. Invest Ophthalmol Vis Sci 46:4788-95
Malek, G; Johnson, L V; Mace, B E et al. (2005) Apolipoprotein E allele-dependent pathogenesis: a model for age-related retinal degeneration. Proc Natl Acad Sci U S A 102:11900-5
Anderson, Don H; Talaga, Kevin C; Rivest, Alexander J et al. (2004) Characterization of beta amyloid assemblies in drusen: the deposits associated with aging and age-related macular degeneration. Exp Eye Res 78:243-56

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