Abstract
Abstract: :
Purpose: To determine the alterations in the gene expression profile of a mouse model of ischemia-induced retinal neovascularization. Methods: Neovascularization was induced in post-natal day seven mice by exposure to hyperoxia for five days and return to normoxia. Retinas were collected from experimental mice and age-matched control mice at post-natal day 18, when neovascularization was maximal. RNA was reverse-transcribed, cRNA was prepared from cDNA, labeled and hybridized to a mouse Affymetrix microarray chip. Microarray results were collected by laser scanning, analyzed and compared against nucleotide and protein databases. Genes were sorted according to their possible pathophysiological significance. Results: The Affymetrix mouse chip U74Av2 contains approximately 6,000 full-length mouse genes and 6,000 expressed sequence tag (EST) clusters from the UniGene database. Twenty nine of the known genes were overexpressed by more than two-fold (range 2-11.1) in the neovascular retinas as compared to the retinas of age-matched controls. Nineteen ESTs were also overexpressed. Twenty two known genes and 34 ESTs were underexpressed more than two fold (range 2-28.4). Among the differentially expressed genes were growth factors and angiogenesis mediator genes. Other genes that were found to be differentially expressed were transcription and cell cycle regulators, metabolic enzymes and signal transduction genes. Comparison of the differentially expressed ESTs to databases did not reveal significant similarities to known genes. Conclusion: Ischemia-induced neovascular retinas were found to differentially express many genes, some of which were previously reported to have a role in retinal angiogenesis or proliferation. Other genes may have a yet unknown role in neovascular pathology. The ESTs may represent novel angiogenesis mediators. The high-throughput gene expression profiling of ischemia-induced retinal neovascularization provides insight into the pathophysiology of the neovascular process, and allows further studies to be initiated towards the identification of new components of the angiogenesis cascade.
Keywords: 566 retinal neovascularization • 572 retinopathy of prematurity • 428 hypoxia