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J.C. Sevilla, M.L. Tapia, A.S. Hackam, R.K. Lee; Lipocalin Expression is Associated With Intraocular Inflammation in DBA2/J Mouse Glaucoma . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1269.
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© ARVO (1962-2015); The Authors (2016-present)
The lipocalins are a family of proteins associated with cell growth, metabolism, immune modulation, and inflammation. The DBA2/J mouse model of glaucoma is associated with pigment dispersion and inflammatory changes in the anterior chamber. These inflammatory changes in the anterior segment of DBA2/J mice include the progressive formation of synechia and increased levels of inflammatory cytokines and activation of inflammation–associated signaling molecules (such as NF–kB). We tested the age–associated expression levels of lipocalin in DBA2/J eyes as a marker for inflammation associated with glaucoma.
Pooled whole retinas from young, non–glaucomatous (< 3 mo. old) and from aged, glaucomatous (≥ 12 mo. old.) DBA2/J mice were homogenized and total RNA was extracted in Triazol using Qiagen RNAEasy separation columns. First strand cDNA was synthesized and used for hybridization to Affymetrix GeneChip Mouse Genome 430 2.0 gene expression microarrays to determine transcriptional levels of lipocalin expression. Quantitative real–time PCR was also used to confirm the microarray gene expression data. Non–glaucomatous age–matched C57/BL6 mouse retinas were also used as controls. Histopathology of young, non–glaucomatous and aged, glaucomatous DBA2/J mice was compared and increasing expression levels of lipocalin were associated with progressive glaucoma, iris atrophy, and retinal ganglion cell loss.
The retinal gene array data was analyzed with Affymetrix Microarray Suite 5.0 and lipocalin was identified as one of the most up–regulated genes differentially expressed in aged, glaucomatous DBA2/J retinas compared to young, non–glaucomatous DBA2/J retinas and to age–matched C57/Bl6 non–glaucomatous controls. This result was confirmed using quantitative real–time PCR. The increase in lipocalin gene expression levels correlated with the histological loss of RGC and iris atrophy in aged, glaucomatous DBA2/J mice.
DBA2/J mice develop chronic progressive glaucoma associated with pigment dispersion. In a genome–wide differential gene expression study of the retinas of DBA2/J mice, lipocalin was discovered to be selectively up–regulated. The increased expression of lipocalin is associated with previously reported increased anterior segment inflammation (elevated inflammatory cytokine and transcription factor expression and pigment dispersion) in the DBA2/J model of glaucoma. Inflammation may play a role in the development of glaucoma in this mouse model.
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