Expression of matrix metalloproteinase-7 in choroidal neovascular membranes in age-related macular degeneration

doi:10.1016/S0002-9394(99)00135-X

American Journal of Ophthalmology

Volume 128, Issue 3, September 1999, Pages 382-384

https://doi.org/10.1016/S0002-9394(99)00135-X Get rights and content

Abstract

PURPOSE:

Matrix metalloproteinases are a family of extracellular matrix-degrading enzymes associated with neovascularization. We evaluated the expression and localization of matrix metalloproteinase-7 in choroidal neovascular membranes in age-related macular degeneration.

METHODS:

Immunofluorescence and transmission electron microscopic examinations were performed on subfoveal neovascular membranes that had been surgically removed from seven eyes of seven patients with age-related macular degeneration.

RESULTS:

Matrix metalloproteinase-7 was expressed in all specimens and distinctly expressed in the thickened layer of Bruch membrane and basement membrane–like structure around retinal pigment epithelial cells.

CONCLUSIONS:

Matrix metalloproteinase-7 was expressed in Bruch membrane of choroidal neovascular membranes in age-related macular degeneration. Matrix metalloproteinase-7 may be an important factor for the development of the submacular neovascular membrane in age-related macular degeneration.

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Citation Excerpt :
Macrophages release cytokines, including vascular endothelial growth factor, when activated, which may contribute to CNV development in AMD patients.69,70 Macrophages also release matrix metalloproteinases,71 which may play a role in the development of CNV in patients with Sorsby Fundus Dystrophy72 and AMD.73–75 In addition to their lipid-lowering effects, statins have anti-inflammatory properties.
To investigate the relationship between statin and aspirin use and the risk of choroidal neovascularization (CNV) in patients with age-related macular degeneration (AMD).
Retrospective consecutive case series.
All patients 60 years and older with AMD who were seen between January 1, 1990, and March 1, 2003, at the San Francisco Veterans Affairs Hospital Eye Clinic with fundus photographs were included. Patients with other diagnoses predisposing to CNV or incomplete medical records were excluded. The main outcome measure was angiographically evident CNV. Diagnosis was based on review of fundus photographs and fluorescein angiograms in masked fashion; medical records were reviewed for variables possibly predisposing to CNV or statin use. For patients with CNV, age of onset was recorded; those without CNV were treated as censored. Age-related macular degeneration disease status and time of onset of CNV was compared between patients treated or not treated with statins for at least 6 months.
Of 326 patients with AMD, 104 had CNV, 204 had dry AMD, and 18 had geographic atrophy (GA). Of CNV subjects, 21 (20%) used statins, compared with 77 (38%) of dry AMD subjects without GA and 6 (33%) of controls with GA (hazard ratio = 0.51, 95% confidence interval (CI) = 0.31–0.86, P = .01). Aspirin use was also significantly associated with decreased rates of CNV; 62 CNV subjects (60%) used aspirin, compared with 154 (75%) dry AMD subjects without GA or 12 (67%) with GA (hazard ratio = 0.63, 95% CI = 0.40–0.98, P = .04).
Therapy with statins or aspirin is associated with decreased rates of CNV among AMD patients. Additional study with a prospective and/or randomized trial of statin and aspirin use in AMD patients is warranted.
Age-related macular degeneration: Etiology, pathogenesis, and therapeutic strategies
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Age-related macular degeneration is the principal cause of registered legal blindness among those aged over 65 in the United States, western Europe, Australia, and Japan. Despite intensive research, the precise etiology of molecular events that underlie age-related macular degeneration is poorly understood. However, investigations on parallel fronts are addressing this prevalent public health problem. Sophisticated biochemical and biophysical techniques have refined our understanding of the pathobiology of drusen, geographic atrophy, and retinal pigment epithelial detachments. Epidemiological identification of risk factors has facilitated an intelligent search for underlying mechanisms and fueled clinical investigation of behavior modification. Gene searches have not only brought us to the cusp of identifying the culpable gene loci in age-related macular degeneration, but also localized genes responsible for other macular dystrophies. Recent and ongoing investigations, often cued by tumor biology, have revealed an important role for various growth factors, particularly in the neovascular form of the condition. Transgenic and knockout studies have provided important mechanistic insights into the development of choroidal neovascularization, the principal cause of vision loss in age-related macular degeneration. This in turn has culminated in preclinical and clinical trials of directed molecular interventions.
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Brief ReportsExpression of matrix metalloproteinase-7 in choroidal neovascular membranes in age-related macular degeneration

Abstract

Ophthalmology

Matrix metalloproteinases and metalloproteinase inhibitors in choroidal neovascular membranes

Invest Ophthalmol Vis Sci

Brief Reports
Expression of matrix metalloproteinase-7 in choroidal neovascular membranes in age-related macular degeneration