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

Abigail S Hackam, Richelle Strom, Dongmei Liu, Jiang Qian, Chenwei Wang, Deborah Otteson, Tushara Gunatilaka, Ronald H. Farkas, Itay Chowers, Masaaki Kageyama, Thierry Leveillard, Jose Alain Sahel, Peter A. Campochiaro, Giovanni Parmigiani, Donald J. Zack

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)2929-2942
Number of pages14
JournalInvestigative Ophthalmology and Visual Science
Volume45
Issue number9
DOIs
StatePublished - Sep 1 2004

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Retinal Degeneration
Gene Expression
Genes
Retinal Rod Photoreceptor Cells
Retina
Retinal Cone Photoreceptor Cells
Vertebrate Photoreceptor Cells
Active Biological Transport
Expressed Sequence Tags
In Situ Hybridization
Real-Time Polymerase Chain Reaction
Oxidative Stress
Animal Models
Complementary DNA
Cell Proliferation
Proteins

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Identification of gene expression changes associated with the progression of retinal degeneration in the rd1 mouse. / Hackam, Abigail S; Strom, Richelle; Liu, Dongmei; Qian, Jiang; Wang, Chenwei; Otteson, Deborah; Gunatilaka, Tushara; Farkas, Ronald H.; Chowers, Itay; Kageyama, Masaaki; Leveillard, Thierry; Sahel, Jose Alain; Campochiaro, Peter A.; Parmigiani, Giovanni; Zack, Donald J.

In: Investigative Ophthalmology and Visual Science, Vol. 45, No. 9, 01.09.2004, p. 2929-2942.

Research output: Contribution to journalArticle

Hackam, AS, Strom, R, Liu, D, Qian, J, Wang, C, Otteson, D, Gunatilaka, T, Farkas, RH, Chowers, I, Kageyama, M, Leveillard, T, Sahel, JA, Campochiaro, PA, Parmigiani, G & Zack, DJ 2004, 'Identification of gene expression changes associated with the progression of retinal degeneration in the rd1 mouse', Investigative Ophthalmology and Visual Science, vol. 45, no. 9, pp. 2929-2942. https://doi.org/10.1167/iovs.03-1184
Hackam, Abigail S ; Strom, Richelle ; Liu, Dongmei ; Qian, Jiang ; Wang, Chenwei ; Otteson, Deborah ; Gunatilaka, Tushara ; Farkas, Ronald H. ; Chowers, Itay ; Kageyama, Masaaki ; Leveillard, Thierry ; Sahel, Jose Alain ; Campochiaro, Peter A. ; Parmigiani, Giovanni ; Zack, Donald J. / Identification of gene expression changes associated with the progression of retinal degeneration in the rd1 mouse. In: Investigative Ophthalmology and Visual Science. 2004 ; Vol. 45, No. 9. pp. 2929-2942.
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abstract = "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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AU - Strom, Richelle

AU - Liu, Dongmei

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AU - Wang, Chenwei

AU - Otteson, Deborah

AU - Gunatilaka, Tushara

AU - Farkas, Ronald H.

AU - Chowers, Itay

AU - Kageyama, Masaaki

AU - Leveillard, Thierry

AU - Sahel, Jose Alain

AU - Campochiaro, Peter A.

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N2 - 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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