endothelin-1 and Macular-Degeneration

The relationship between ischemic vascular disease and age-related macular degeneration may indicate the role of vascular injury as the primary insult causing functional deficits in age-related macular degeneration. The vasoactive factors produced by endothelial cells include endothelin-1 (ET-1), which is one of the most potent vasoconstricting peptides. In this study we sought to explore the potential role of endothelial dysfunction in the pathogenesis of age-related macular degeneration by measuring the concentration of ET-1 in peripheral blood of individuals diagnosed with age-related macular degeneration and evaluating its intracellular expression in peripheral blood cells, on mRNA level.. Peripheral blood samples from 31 patients with diagnosed dry age-related macular degeneration and 46 patients with neovascular age-related macular degeneration were collected. Forty six age- and sex-matched volunteers without age-related macular degeneration were enrolled as a control group. ET-1 plasma levels were analyzed by ELISA and intracellular expression of ET-1 in peripheral blood cells was studied by using qRT-PCR.. The expression of intracellular ET-1 was significantly elevated in peripheral blood cells of both dry and wet age-related macular degeneration patients compared with the control subjects. Immunofluorescence staining revealed that ET-1 was specifically expressed in the circulating endothelial cells.. We assume that damaged endothelial cells may release a variety of vasoconstricting molecules, including ET-1, leading to derangement between the endothelium-derived relaxing and contracting factors. Local retinal ischemia consequently develops which may promote the development of retinal degeneration in patients with age-related macular degeneration,

Topics: Aged; Aged, 80 and over; Biomarkers; Early Diagnosis; Endothelin-1; Enzyme-Linked Immunosorbent Assay; Female; Humans; Macular Degeneration; Male; Middle Aged; Risk Factors

Circulating endothelial cells (CECs) and endothelial progenitor cells (EPCs) may serve as novel markers of endothelial dysfunction. The presence and clinical implications of CECs and the expression of endothelin (ET)-1, one of the most potent vasoconstrictors, have not been evaluated in patients with the neovascular form of age-related macular degeneration (AMD). This study was conducted to determine the different populations of endothelial cells (ECs) in the peripheral blood of AMD patients and to correlate these findings with the expression of ET-1 and the cytokines and growth factors responsible for EC migration and function.. Peripheral blood samples were collected from 29 patients with diagnosed neovascular AMD and from 38 healthy control subjects. CD133(-)CD144(+) CECs and CD34(+)CD133(+)CD144(+) EPCs were counted and analyzed by flow cytometry. The intracellular expression of ET-1 in peripheral blood nuclear cells (PBNCs) was studied by using qRT-PCR, Western blot, and immunocytofluorescence assays, and ET-1, IGF-1, VEGF, SDF-1, and HGF plasma concentrations were measured in enzyme-linked immunosorbent assays.. Increased CECs and EPCs were found in the AMD patients compared with the counts in healthy individuals. The expression of intracellular ET-1 was significantly elevated in PBNCs from the AMD patients compared with the control subjects. In addition a significantly higher plasma concentration of IGF-1 was observed, but a lower SDF-1 level in the group of AMD patients.. These findings suggest that circulating endothelial cells, together with high ET-1 content, may contribute to the development of AMD. Further prospective investigations on the mechanism involved may be relevant to the potential treatment of this disease.

Topics: Aged; Antigens, CD; Blood Circulation; Blotting, Western; Cytokines; Endothelin-1; Endothelium, Vascular; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Fluorescent Antibody Technique, Indirect; Hematopoietic Stem Cells; Humans; Insulin-Like Growth Factor I; Macular Degeneration; Male; Reverse Transcriptase Polymerase Chain Reaction; Vascular Endothelial Growth Factor A

Topics: Aged; Aged, 80 and over; Biomarkers; Choroidal Neovascularization; Endothelin-1; Female; Humans; Macular Degeneration; Male; Middle Aged; Prognosis; Severity of Illness Index