Abstract
Abstract: :
Purpose: BMPs, BMP receptors and BMP associated proteins are expressed in the human TM and ONH, and bmp 4+/– mice have been reported to develop elevated IOP and ON abnormalities. The purpose of this study is to characterize and compare changes in gene expression of human trabecular meshwork cells (HTM), lamina cribrosa cells (LC) and optic nerve head astrocytes (ONHA) in response to exogenous BMP4. Methods: Human TM cells, LC cells and ONHAs were exposed to either vehicle or BMP4(20 ng/ml) for 24 and 72 hours, and total RNA was extracted using Trizol.Affymetrix Human Genome U133 Gene Chip and UIMaDS were used to evaluate and compare changes in gene expression. Results: A total of 39,000 genes and expressed sequence tags(EST) were examined.The data were filtered according to statistically significant changes in gene expression as well as a 2– fold or greater change in gene expression.In TM cells after 24 hours exposure to BMP4, a total of 105 genes were upregulated and 42 genes were downregulated.In LC cells after 24 hours exposure to BMP4,a total of 278 genes were upregulated and 118 genes were downregulated.In ONHA after 72 hours exposure to BMP4,48 genes were upregulated and 193 genes were downregulated.Categories of genes with BMP4–induced altered gene expression included:(A)extracellular matrix/cytoskeletal,(B)growth factors and growth factor receptors and (C)signaling pathways. Conclusions: These gene microarray data revealed BMP4–induced changes in gene expression for a number of genes,including extracellullar matrix/cytoskeletal components and growth factor related genes.The simultaneous screening of thousands of genes by the Microarray analysis will help identify gene(s) primarily involved in BMP signaling and will enhance our understanding of the role of bone morphogenetic proteins in the normal regulation of tissues involved in the pathogenesis of glaucoma.
Keywords: gene microarray • growth factors/growth factor receptors • extracellular matrix