May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Identification of Molecular Pathways Leading to the Prcd Phenotype Using cDNA Expression Profiling
Author Affiliations & Notes
  • B. Zangerl
    Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania
  • K. E. Guziewicz
    Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania
  • G. L. Paez
    Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania
  • S. J. Lindauer
    Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania
  • G. M. Acland
    J.A. Baker Institute, Cornell University, Ithaca, New York
  • G. D. Aguirre
    Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania
  • Footnotes
    Commercial Relationships B. Zangerl, None; K.E. Guziewicz, None; G.L. Paez, None; S.J. Lindauer, None; G.M. Acland, None; G.D. Aguirre, None.
  • Footnotes
    Support FFB; MAF/TSE, Inc.; EY06855; EY13132; Van Sloun Fund; L.J.Niles Found.; ONCE Int’l Prize; URF Award
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 3709. doi:
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      B. Zangerl, K. E. Guziewicz, G. L. Paez, S. J. Lindauer, G. M. Acland, G. D. Aguirre; Identification of Molecular Pathways Leading to the Prcd Phenotype Using cDNA Expression Profiling. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3709.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose:: Progressive rod-cone degeneration (prcd), an animal model for human ARRP, is caused by a mutation in the second codon of PRCD. The function of the gene, or the pathway(s) responsible for the disease phenotype, are still unclear. The expression profile of prcd was established at time points significant to the degenerative process (10, 16, and 24 weeks) and compared to expression in age matched normal retinas, and those with mutations in RPGR, establishing changes unique to the PRCD mutation.

Methods:: We recently established retinal expression profiles in normal and RPGR2 affected retinas using a canine, custom-made, retinal cDNA microarray. This array has now been expanded by another 10,000 clones after subtraction of the original cDNA library, thus increasing the number of uniquely expressed transcripts by ~7,000. The second generation microarray was used to examine the expression pattern of prcd affected and age-related normal retinas. Analyses were performed using principal component analysis (PCA) and SAM.

Results:: The expression profiles of normal retinas, previously examined at 3, 7, and 16 weeks, were extended by 10 and 24 week old individuals. A series of genes were confirmed to contribute to retinal development and maintenance, and these changed with age. PRCD affected retinas showed distinctly different expression profiles at each age examined; changes with age reflected alterations associated with the disease process. Comparison to the expression specific for mutations in the RPGR gene (XLPRA1 and XLPRA2) filtered those genes to identified a prcd- specific profile.

Conclusions:: Changes in retinas of 10, 16, and 24 weeks that are unique to prcd allowed to establish marker genes to define molecular changes relevant to the disease. Based on the differences in the degeneration rate of the superior und inferior half of prcd affected retinas, the expression profiles are followed up with topological correlation to those areas. The combined information allows formulating hypotheses on the pathophysiology of the disease, and identifying key molecules to examine the degenerative process at the molecular level.

Keywords: retinal degenerations: hereditary • gene microarray • gene/expression 
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