Identification of gene expression changes associated with the progression of retinal degeneration in the rd1 mouse

被引:84
作者
Hackam, AS
Strom, R
Liu, DM
Qian, J
Wang, CW
Otteson, D
Gunatilaka, T
Farkas, RH
Chowers, I
Kageyama, M
Leveillard, T
Sahel, JA
Campochiaro, PA
Parmigiani, G
Zack, DJ
机构
[1] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Guerrieri Ctr Genet Engn & Mol Ophthalmol, Baltimore, MD 21287 USA
[2] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Dept Ophthalmol, Baltimore, MD 21287 USA
[3] Johns Hopkins Univ, Sch Med, Dept Biostat, Baltimore, MD 21287 USA
[4] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21287 USA
[5] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21287 USA
[6] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21287 USA
[7] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21287 USA
[8] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21287 USA
[9] Santen Pharmaceut Co Ltd, Takayama, Japan
[10] Hop St Antoine, F-75571 Paris, France
关键词
D O I
10.1167/iovs.03-1184
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
PURPOSE. One approach to gaining insight into the biological pathways contributing to rod and cone photoreceptor death is to identify patterns of gene expression changes. In the present study, a custom retinal microarray was developed to analyze the rd1 mouse, a well-characterized animal model of human retinal degeneration. METHODS. A microarray was constructed containing cDNA fragments corresponding to genes known or postulated to be involved in normal retinal function, development, and disease. Gene expression in rd1 retina was compared with age-matched control retinas at three time points: the peak of rod degeneration (postnatal day [P]14), early in cone degeneration (P35), and during cone degeneration (P50). Selected microarray results were confirmed with real-time PCR. The cellular distribution of one of the differentially expressed genes, dickkopf 3 (Dkk3), was assessed by in situ hybridization. RESULTS. At each stage of degeneration, there was only limited overlap of the genes that showed increased expression, suggesting the involvement of temporally distinct molecular pathways. Genes active in transport mechanisms and in signaling pathways were differentially expressed during rod degeneration, whereas genes with functions in protein modification and cellular metabolism were differentially expressed during cone degeneration. Increased expression of genes involved in cell proliferation pathways and oxidative stress was observed at each time point. CONCLUSIONS. These microarray results provide clues to understanding the molecular pathways underlying photoreceptor degeneration and indicate directions for future studies. In addition, comparisons of normal and degenerated retina identified numerous genes and ESTs that are potentially enriched in rod photoreceptors.
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页码:2929 / 2942
页数:14
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