Identifizierung von Kandidaten-Genen altersabhängiger Makuladegeneration (AMD) und familiärer Formen von Netzhauterkrankungen (Identification of candidate genes for age-related macular degeneration (AMD) and familial forms of retinal dystrophies)

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During the last years, molecular genetic studies unraveled a number of gene defects underlying monogenic forms of macular dystrophies. However, patients with age-related macular degeneration (AMD) did not show disease-associated mutations these genes. A different approach to identify genetic risk factors for AMD represents the analysis of candidate genes which are either specifically expresed in the retina, retinal pigment epithelium (RPE), and/or choroid, or have an important function in these tissues. Here we propose to identify and characterize novel, eye-specific gene transcripts, which are differentially expressed as a result of degenerative and proliferative processes in the retina and adjacent tissues. Eye-tissues will be obtained from a mutant mouse line which was established by gene targeting of the Norrie disease (ND) gene. Morphological analysis of the eyes showed characteristic changes in the retina of affected animals, predominantly in ganglion cells and the inner nuclear layer which contains the intermediate neurons. The photoreceptor cells show only focal abnormalities. Differentially expressed genes will be isolated by a gene subtraction protocol and classified in two groups, depending on the orientation of the subtraction: 1. transcripts which are downregulated or eliminated in the degeneration retina and 2. those mrNAs which are abundantly expressed in response to tissue damage or as a result of cell proliferation. The human orthologues of these mouse genes will be identified, mapped in the genome and will be analyzed as candiate genes for AMD as well as familial forms of vision defects.