Retinal degeneration, genetic

Edwards, AO, 2008. Genetics of age-related macular degeneration. Recent Advances in Retinal Degeneration 613, 211-219. 

Wells J, Wroblewski J, Keen J, Inglehearn C, Jubb C, et al. 1993. Mutations in the human retinal degeneration slow (RDS) gene can cause either retinitis pigmentosa or macular dystrophy (see comments). Nat Genet 3 213-218. 

Successful application of ocular gene therapy has been demonstrated in animal diseases or animal models of human disease. The most encouraging results in the field of ocular gene therapy involve treatment of genetically inherited retinal degenerations occurring in various animal species. Conventional pharmacologic approaches... 

Ali R, Sarra GM, Stephens C, et al. Restoration of photoreceptor ultrastructure and function in retinal degeneration slow mice by gene therapy. Nature Genet 2000 25 306-310. 

The cellular distribution of enzyme and the nature of enzyme protein were thought to be governed by genetic factors. Another interesting discovery is that the relationship between the mutant retinal degeneration and low /3-giucuronidase in mice has been clarified. 

Wang, X, A.M. Lawler, G. Steel, I. Sipila, A.H. Milam, and D. Valle, 1995. Mice lacking omithine-delta-amino-transferase have paradoxical neonatal hypoomithinaemia and retinal degeneration. Nat. Genet. 11, 185-190. Watford, M, 1994. Glirtartrine-metabolism in rat small-intestine - synthesis of 3-carbon products in isolated enterocyles. Biochim. Biophys. Acta 1200, 73-78. 

Heritable and spontaneous genetic disorders represent additional applications for therapeutic ribozymes targeting cellular genes. These include the beta-amyloid peptide precursor mRNA involved in Alzheimer s disease (Currie et al., 1997 Dolzhanskaya et al., 2000), and an autosomal-dominant point mutation in the rhodopsin mRNA that gives rise to photoreceptor degeneration and retinitis pigmentosa (Hauswirth and Lewin, 2000 LaVail et al., 2000). 

Leber hereditary optic neuropathy (LHON) is the most common mitochondrial disease and the first linked to maternal inheritance through a mutation in the mtDNA. LHON is characterized by bilateral subacute loss of central vision caused by focal degeneration of the retinal ganglion cell layer and of the optic nerve. After initial symptoms, both eyes are usually affected within 6 months. Approximately 50% to 60% of males and only 8% to 32% of females who possess the mtDNA mutation will actually develop this optic neuropathy. Nuclear-encoded factors that affect mtDNA expression, mtDNA products, or mitochondrial metabolism may modify the phenotypic expression of LHON. Genetic coimseling in LHON is complicated in that the amount of mutant mtDNA transmitted by heteroplasmic females cannot be predicted, and testing cannot predict which individuals will develop visual symptoms. ... 

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