Email updates

Keep up to date with the latest news and content from Genome Biology and BioMed Central.

Open Access Research

Susceptibility to glaucoma: differential comparison of the astrocyte transcriptome from glaucomatous African American and Caucasian American donors

Thomas J Lukas1*, Haixi Miao2, Lin Chen2, Sean M Riordan2, Wenjun Li2, Andrea M Crabb2, Alexandria Wise3, Pan Du4, Simon M Lin4 and M Rosario Hernandez2

Author Affiliations

1 Department of Molecular Pharmacology and Biological Chemistry, Feinberg School of Medicine, Northwestern University, E Chicago Ave, Chicago, IL 60611 USA

2 Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, E Chicago Ave, Chicago, IL 60611 USA

3 Department of Biology, City College of New York, Convent Ave, New York, NY 10031, USA

4 Robert H Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, E Chicago Ave, Chicago, IL 60611 USA

For all author emails, please log on.

Genome Biology 2008, 9:R111  doi:10.1186/gb-2008-9-7-r111

Published: 9 July 2008

Abstract

Background

Epidemiological and genetic studies indicate that ethnic/genetic background plays an important role in susceptibility to primary open angle glaucoma (POAG). POAG is more prevalent among the African-descent population compared to the Caucasian population. Damage in POAG occurs at the level of the optic nerve head (ONH) and is mediated by astrocytes. Here we investigated differences in gene expression in primary cultures of ONH astrocytes obtained from age-matched normal and glaucomatous donors of Caucasian American (CA) and African American (AA) populations using oligonucleotide microarrays.

Results

Gene expression data were obtained from cultured astrocytes representing 12 normal CA and 12 normal AA eyes, 6 AA eyes with POAG and 8 CA eyes with POAG. Data were normalized and significant differential gene expression levels detected by using empirical Bayesian shrinkage moderated t-statistics. Gene Ontology analysis and networks of interacting proteins were constructed using the BioGRID database. Network maps included regulation of myosin, actin, and protein trafficking. Real-time RT-PCR, western blots, ELISA, and functional assays validated genes in the networks.

Conclusion

Cultured AA and CA glaucomatous astrocytes retain differential expression of genes that promote cell motility and migration, regulate cell adhesion, and are associated with structural tissue changes that collectively contribute to neural degeneration. Key upregulated genes include those encoding myosin light chain kinase (MYLK), transforming growth factor-β receptor 2 (TGFBR2), rho-family GTPase-2 (RAC2), and versican (VCAN). These genes along with other differentially expressed components of integrated networks may reflect functional susceptibility to chronic elevated intraocular pressure that is enhanced in the optic nerve head of African Americans.