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Age-related Macular Degeneration. Clinical, Pathologic and Experimental Findings
Grossniklaus H. E.,
Emory University School of Medicine, Department of Ophthalmology (Atlanta)
Purpose: To review the clinicopathologic findings and ongoing research of age-related macular degeneration with implications regarding the pathobiology of the disease.
Methods: Review of past clinicopathologic correlations and ongoing research performed in the L.F. Montgomery Laboratory, Emory University, Atlanta, Georgia.
Results: Age-related macular degeneration (ARMD) occurs in 9% of the population and is found in 33% of autopsy eyes from patients over 65 years old. The two general categories of ARMD are exudative (dry) and non-exudative (wet). Exudative ARMD is associated with choroidal neovascularization (CNV). Soft, large and confluent drusen are all associated with ARMD. The amount of and presence of basal laminar deposit (BlamD) and basal linear deposit (BlinD) strongly correlate with ARMD. Two general growth patterns of CNV occur: sub-RPE (type 1) and subretinal (type 2). It may be possible to distinguish the type 1 and type 2 patterns by fundus examination. Two general angiographic patterns of CNV occur: classic and occult. It is possible to correlate pathologic specimens with classic and occult angiographic CNV. Histologic, immunohistochemical, and ultrastructural studies have shown that CNV represents a stereotypic, non-specific wound repair response to a specific stimulus. Our laboratory has demonstrated that BlinD-like material accumulates in Bruch's membrane of genetically or environmentally induced hypercholesterolemic mice. Additionally, if the RPE of the mice is compromised by photochemical injury, they accumulate BlamD-like material. This BlamD-like may be related to lipid metabolism at the level of the RPE. We have recently demonstrated by RT PCR that mRNA for proteins involved with lipid metabolism, ACAT1, ACAT2 and ABCA-1, are expressed in human and murine RPE. We have also demonstrated by Western blot analysis and in-situ hybridization that ABCA-1 is expressed in human RPE.
Conclusions: These findings enable us to search for mutations in the genes or abnormalities in the protein that may be involved in the pathobiology of age-related macular degeneration.