): Age-related macular degeneration (ARMD) is a progressive disorder of the retina occurring in people older than age 50 associated with vision loss coupled with a spectrum of specific clinical, physiological and histopathological features. The pathogenic mechanisms for these specific changes are unknown, but circumstantial evidence suggests a role for a macrophage-mediated component in ARMD. We propose the general hypothesis that choroidal macrophages observed in ARMD are blood-derived monocytes recruited to the choriocapillaris to scavenge debris and deposits trapped in Bruch's membrane. In this project, we propose two specific aims to explore macrophage activation under conditions relevant to ARMD.
In aim 1, we will use freshly isolated blood monocytes from normal subjects or ARMD patients, to establish the existence of high and low activity monocytes and to determine if high activity is a prognostic marker for ARMD progression.
In aim 2, using a mouse model for age-related subRPE extracellular deposit formation recently developed in our laboratory, we will induce high activity monocytes in mice and establish that these macrophages will increase the severity of RPE degeneration or rate of progression of deposit formation.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
1R01EY013318-01
Application #
6258600
Study Section
Visual Sciences C Study Section (VISC)
Program Officer
Dudley, Peter A
Project Start
2001-02-01
Project End
2004-01-31
Budget Start
2001-02-01
Budget End
2002-01-31
Support Year
1
Fiscal Year
2001
Total Cost
$303,000
Indirect Cost
Name
University of Miami School of Medicine
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
City
Miami
State
FL
Country
United States
Zip Code
33146
Marin-Castano, Maria E; Csaky, Karl G; Cousins, Scott W (2005) Nonlethal oxidant injury to human retinal pigment epithelium cells causes cell membrane blebbing but decreased MMP-2 activity. Invest Ophthalmol Vis Sci 46:3331-40
Espinosa-Heidmann, Diego G; Marin-Castano, Maria E; Pereira-Simon, Simone et al. (2005) Gender and estrogen supplementation increases severity of experimental choroidal neovascularization. Exp Eye Res 80:413-23
Caicedo, Alejandro; Espinosa-Heidmann, Diego G; Hamasaki, Duco et al. (2005) Photoreceptor synapses degenerate early in experimental choroidal neovascularization. J Comp Neurol 483:263-77
Espinosa-Heidmann, Diego G; Reinoso, Maria A; Pina, Yolanda et al. (2005) Quantitative enumeration of vascular smooth muscle cells and endothelial cells derived from bone marrow precursors in experimental choroidal neovascularization. Exp Eye Res 80:369-78
Caicedo, Alejandro; Espinosa-Heidmann, Diego G; Pina, Yolanda et al. (2005) Blood-derived macrophages infiltrate the retina and activate Muller glial cells under experimental choroidal neovascularization. Exp Eye Res 81:38-47
Cousins, Scott W; Espinosa-Heidmann, Diego G; Csaky, Karl G (2004) Monocyte activation in patients with age-related macular degeneration: a biomarker of risk for choroidal neovascularization? Arch Ophthalmol 122:1013-8
Espinosa-Heidmann, Diego G; Sall, John; Hernandez, Eleut P et al. (2004) Basal laminar deposit formation in APO B100 transgenic mice: complex interactions between dietary fat, blue light, and vitamin E. Invest Ophthalmol Vis Sci 45:260-6
Suner, Ivan J; Espinosa-Heidmann, Diego G; Marin-Castano, Maria E et al. (2004) Nicotine increases size and severity of experimental choroidal neovascularization. Invest Ophthalmol Vis Sci 45:311-7
Miller, Daniel M; Espinosa-Heidmann, Diego G; Legra, Jessica et al. (2004) The association of prior cytomegalovirus infection with neovascular age-related macular degeneration. Am J Ophthalmol 138:323-8
Espinosa-Heidmann, Diego G; Suner, Ivan J; Hernandez, Eleut P et al. (2003) Macrophage depletion diminishes lesion size and severity in experimental choroidal neovascularization. Invest Ophthalmol Vis Sci 44:3586-92

Showing the most recent 10 out of 13 publications