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


CONCLUSIONS
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-beta 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.
Lukas
Thomas J
TJ
Department of Molecular Pharmacology and Biological Chemistry, Feinberg School of Medicine, Northwestern University, E Chicago Ave, Chicago, IL 60611, USA. t-lukas@northwestern.edu
Miao
Haixi
H
Chen
Lin
L
Riordan
Sean M
SM
Li
Wenjun
W
Crabb
Andrea M
AM
Wise
Alexandria
A
Du
Pan
P
Lin
Simon M
SM
Hernandez
M Rosario
MR
D001741:Black or African American / Q000235:genetics*; D000368:Aged; D001253:Astrocytes / Q000378:metabolism* / Q000502:physiology; D002465:Cell Movement; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005123:Eye; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D020022:Genetic Predisposition to Disease; D005902:Glaucoma, Open-Angle / Q000208:ethnology* / Q000235:genetics* / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D009900:Optic Nerve / Q000166:cytology; D021381:Protein Transport; D015398:Signal Transduction; D014019:Tissue Donors; D044465:White People / Q000235:genetics*
D000242:Cyclic AMP