title: From disease genes to cellular pathways: a progress report.
abstract: Mutations in a large number of retinal and retinal pigment epithelium (RPE) expressed genes can lead to the degeneration of photoreceptors and consequently the loss of vision. The genetic and phenotypic heterogeneity of retinal dystrophies poses a complex problem with respect to rational development of therapeutic strategies. Delineation of physiological functions of disease genes and identification of pathways that lead to disease pathogenesis represent essential goals towards developing a systematic and global approach to gene-based treatments. We are interested in identifying cellular pathways that are involved in photoreceptor differentiation, function and degeneration. We are, therefore, generating comprehensive gene expression profiles of retina and RPE of humans and mice using both cDNA- and oligonucleotide-based (Affymetrix) microarrays. Because of the under-representation of retinal/RPE genes in the public databases, we have constructed several unamplified cDNA libraries and produced almost twenty thousand expressed sequence tags (ESTs) that are being printed onto glass slides ('I-Gene' microarrays). In this presentation, we will report the microarray analysis of the rodless (and cone-enhanced) retina from the Nrl-knockout mouse as a paradigm to initiate the identification of cellular pathways involved in photoreceptor differentiation and function.
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 48105-0714, USA.
authors.forename: J
authors.initials: J
authors.lastname: Yu
authors.forename: A J
authors.initials: AJ
authors.lastname: Mears
authors.forename: S
authors.initials: S
authors.lastname: Yoshida
authors.forename: R
authors.initials: R
authors.lastname: Farjo
authors.forename: T A
authors.initials: TA
authors.lastname: Carter
authors.forename: D
authors.initials: D
authors.lastname: Ghosh
authors.forename: A
authors.initials: A
authors.lastname: Hero
authors.forename: C
authors.initials: C
authors.lastname: Barlow
authors.forename: A
authors.initials: A
authors.lastname: Swaroop
mesh_terms: D004268:DNA-Binding Proteins / Q000378:metabolism; D005136:Eye Proteins / Q000378:metabolism; D030342:Genetic Diseases, Inborn / Q000235:genetics / Q000378:metabolism*; D008660:Metabolism / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010802:Phylogeny; D012164:Retinal Diseases / Q000188:drug therapy / Q000517:prevention & control
chemical_list: D004268:DNA-Binding Proteins; D005136:Eye Proteins