Abstract
Purpose: :
Recent studies have revealed an association between coronary risk factors and the appearance of age related macular degeneration (AMD). Early AMD is characterized by changes in the retinal pigment epithelium (RPE) like cell loss, advanced senescence, increased growth factors expression and extracellular matrix (ECM) accumulation. Similar mechanisms occur in atherosclerosis, in which uptake of oxidized low density lipoprotein (Ox_LDL) by macrophages via scavenger receptor involves the initial lesion. It has been previously shown that OX–LDL and scavenger receptors are also present in the RPE. Therefore we investigated the effect of Ox–LDL on the early cellular key events of AMD.
Methods: :
Cultivated RPE cells from 5 human donors of the third passage were incubated with 10–100 µg Ox–LDL. Cell loss was investigated by life dead assay. For determination of advanced senescence beta galactosidase staining was used. The expression of the growth factor TGF–beta was analyzed by an ELISA assay. The induction of collagen type IV, laminin and fibronectin were quantified by western and northern blot analysis.
Results: :
Ox–LDL markedly induced cell death of cultured RPE cells and accelerated the onset of RPE senescence, whereas LDL showed no effect. Expression of TGF–beta was increased by Ox–LDL (400 pg/ml +/– 45) and LDL (195 pg/ml +/– 24). Furthermore Ox–LDL induced ECM proteins (collagen type IV 190%, laminin 145 % and fibronectin 170 %) on the mRNA and protein level. LDL treatment showed similar results.
Conclusions: :
OX–LDL and LDL seems to induce early cellular events of AMD in the RPE. Therefore it is likely, that optimisation of atherosclerotic risk factors could reduce the prevalence of early AMD.
Keywords: age-related macular degeneration • lipids • retinal pigment epithelium