Abstract
Purpose: :
Anterior uveitis, pigment dispersal from iris-ciliary body, and retinal ganglion cell death are cardinal signs of pigment dispersion syndrome in DBA/2J mice. While extensive studies on retina have been reported, little is known about gene expression in the anterior segment of the eye in the course of the disease. We investigated gene expression profiling of iris and ciliary body of DBA/2J mice in the course of development of pigmentary glaucoma.
Methods: :
Iris and cilary bodies of DBA/2J mice at age of 2-3, 6 and 9 months were isolated and RNA was prepared from those tissues. Eyes of C57/BL6 mice of matched age were used as controls. Gene expression profiles were determined by RNA microarray assay using Agilent Mouse Oligo Microarray and analyzed by Ingenuity Pathway Analysis. Changes of gene expression were also tested with quantitative real-time polymerase chain reaction (QRT-PCR) and immunohistochemistry.
Results: :
Expression of 1306 genes in the aged mice showed at least two fold changes (p<0.05) (of which 743 genes showed an increased-expression while 563 genes showed down-regulated expression) as compared with the young mice. Most of genes that were up-regulated were associated with inflammation, immune responses, and leukocyte trafficking (including TNF-alpha and CCL8). The changes of gene expression were confirmed by QRT- PCR and immunohistochemistry.
Conclusions: :
Group of genes that are responsible for host defense, inflammation and cell trafficking are up-regulated in the iris and ciliary bodies of DBA/2J mouse eyes as they develop pigment dispersion syndrome. Gene microarray assay provides us with a powerful tool to understand molecular basis of the pathogenesis of pigment dispersion syndrome in DBA/2J mice.
Keywords: gene microarray • inflammation • iris