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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Investigation of the potential utility of a linomide analogue for treatment of choroidal neovascularization
Experimental Eye Research, Volume 91, No. 6, Year 2010
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Description
The aim of this study was to test the selectivity, in-vivo effectiveness, and potential mechanism of action of a linomide analogue (N-phenyl-1,2-dihydro-4-hydroxyl-2-oxo-quinoline-3-carboxamide, Lin05) for inhibition of choroidal neovascularization. The selectivity of Lin05 was tested in cell proliferation assays with human umbilical vein endothelial cells (HUVEC) and a retinal pigmented epithelial cell line(ARPE-19). In-vivo anti-angiogenic effect of Lin05 was investigated utilizing an experimental laser-induced choroidal neovascularization (ECNV) model in adult Brown Norway rats. Western blot and/or reverse transcriptase-PCR was used to test the effect of Lin05 on potential targets. Our results indicate that Lin05 is at least an 8-fold more selective inhibitor of endothelial cell proliferation compared to RPE cells. Systemic administration of Lin05 in an ECNV model was associated with a significant decrease in both vascular leakage on fluorescein angiography and lesion size by histopathology (p = 0.02). No systemic toxicity was detected for Lin05 in major organs such as the liver, lung and kidneys. Lin05 did not inhibit VEGF-induced VEGFR2 (KDR) phosphorylation in HUVEC nor was associated with decreased VEGF gene expression. Also it did not inhibit insulin-like growth factor (IGF-1) and Epidermal Growth Factor (EGF) induced activation of p42/p44 MAPK activation. It inhibited both PDGF- and bFGF-induced p42/p44 MAPK phosphorylation. However, the effect on PDGF was variable in different HUVEC cells. In conclusion, Lin05 is a potential anti-angiogenic agent for the treatment of eye diseases associated with pathological neovascularization. The anti-angiogenic effect of Lin05 is likely through inhibition of bFGF but not through inhibition of the VEGF/KDR pathway. © 2010.
Authors & Co-Authors
Abdel-Rahman, Mohamed H.
United States, Columbus
The Ohio State University
Yang, Y.
United States, Columbus
The Ohio State University
Salem, Manar M.
United States, Columbus
The Ohio State University
Egypt, Tanta
Tanta University
Meadows, S.
United States, Columbus
The Ohio State University
Massengill, James B.
United States, Columbus
The Ohio State University
Li, P. K.
United States, Columbus
The Ohio State University
Davidorf, Frederick H.
United States, Columbus
The Ohio State University
Statistics
Citations: 7
Authors: 7
Affiliations: 2
Identifiers
Doi:
10.1016/j.exer.2010.10.013
ISSN:
00144835
Research Areas
Genetics And Genomics
Health System And Policy