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J. Feher, M. Artico, I. Kovacs, A. Papale, C. Balacco Gabrieli; Role of Choriocapillaries and Macrophages in the Pathology of Early AMD. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5170.
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Abnormal lipid metabolism plays a central role in the pathogenesis of AMD. Recent observations suggested that inflammation may be a significant contributing factor to the pathology of AMD. The aim of our study was to reveal pathological alterations of choriocapillaries and macrophages related to the inflammation in early AMD
Electron microscopic and histochemical studies were performed on 65 enucleated human eyes aged from 42 to 87: A particular attention was paid to the correlation between cellular (RPE, endothelium, macrophage) and Bruch’s’ membrane changes related to aging and AMD. Quantitative changes were evaluated by the use of computer assisted morphometric analysis.
In this unique human material, we found some previously not described characteristic alterations in early AMD (1) Accumulation of lipofuscin, decrease in number of mitochondria and alterations of mitochondrial membranes in RPE, as well as deposition of lipids or lipid-containing structures of various morphology and density in the Bruch’s membrane, were associated with proliferation of peroxisomes in the RPE; (2) Progressive age-related thickening of both RPE and choriocapillary basement membrane was accompanied with an increase in lipids and glycated proteins. These alterations were significantly more marked in AMD. (3) Capillary endothelium and its basement membrane formed special structural organization, called "invasoma" and characterized by (i) widening of cytoplasm and loss of fenestration, (ii) protrusion of the cytoplasm into the underlying basement membrane, (iii) increased density of adjacent cytoplasm, (iv) increase in ER in the cytoplasm, and (v) focal dissolution of the underlying basement membrane. (4) In some specimens direct contact between endothelial cells and mononuclear cells were observed. In that places both cells formed "contact site" on their plasma membrane characterized by focal electron-density. In addition, extravasation of mononuclear cells into the Bruch’s membrane was also observed. (5) Cytoplasmic processes of unknown origin were also found in the outer collageneous layer.
Our electron microscopic observations clearly demonstrated that choriocapillaries and macrophages may play an essential role in the elimination of metabolic by-products coming from the altered renewal of photoreceptor cells. In humans, this is the first morphological demonstration of contacts between a local pathology and the immune system suggesting a new target for treating early AMD.
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