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2. Local administration of an adeno-associated viral vector expressing IL-10 reduces monocyte infiltration and subsequent photoreceptor damage during experimental autoimmune uveitis.

Author

Broderick CA, Smith AJ, Balaggan KS, Georgiadis A, Buch PK, Trittibach PC, Barker SE, Sarra GM, Thrasher AJ, Dick AD, and Ali RR

Subjects
Animals, Autoimmune Diseases immunology, Female, Genetic Vectors therapeutic use, Interleukin-10 genetics, Interleukin-10 metabolism, Mice, Mice, Inbred C57BL, Monocytes drug effects, Monocytes physiology, Retinal Degeneration, Uveitis immunology, Autoimmune Diseases therapy, Dependovirus genetics, Genetic Therapy, Interleukin-10 therapeutic use, Photoreceptor Cells, Vertebrate immunology, Uveitis therapy
Abstract

Autoimmune posterior uveitis is a chronic, potentially blinding inflammatory disease of the eye. It is commonly treated with immunosuppressive drugs that have adverse long-term effects. Advances in gene transfer techniques have enabled long-term, stable transduction of retinal cells following subretinal injection with adeno-associated viral (AAV) vectors. Here we report for the first time that subretinal injection of rAAV-2 encoding murine IL-10 into the retina of C57BL/6 mice significantly decreases the median experimental autoimmune uveitis (EAU) disease severity. This protection is shown to be due to a decrease in the number and activation status of infiltrating monocytes during EAU, as determined by costimulatory molecule expression and nitrotyrosine detection. No differences within splenocyte proliferative responses or serum antibody levels were detected, emphasizing the potential of gene therapy strategies in ameliorating autoimmune responses in local microenvironments without unwanted systemic effects.

Published
2005
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3. DFNA25, a novel locus for dominant nonsyndromic hereditary hearing impairment, maps to 12q21-24.

Author

Greene CC, McMillan PM, Barker SE, Kurnool P, Lomax MI, Burmeister M, and Lesperance MM

Subjects
Adult, Age of Onset, Child, Preschool, Chromosome Mapping, Czechoslovakia ethnology, Female, Gene Frequency genetics, Haplotypes genetics, Hearing Loss, Sensorineural epidemiology, Humans, Lod Score, Lymphocytes, Male, Models, Genetic, Pedigree, Penetrance, Presbycusis genetics, Syndrome, United States, Chromosomes, Human, Pair 12 genetics, Genes, Dominant genetics, Hearing Loss, Sensorineural genetics
Abstract

Using linkage analysis, we identified a novel dominant locus, DFNA25, for delayed-onset, progressive, high-frequency, nonsyndromic sensorineural hearing loss in a large, multigenerational United States family of Czech descent. On the basis of recombinations in affected individuals, we determined that DFNA25 is located in a 20-cM region of chromosome 12q21-24 between D12S327 (centromeric) and D12S84 (telomeric), with a maximum two-point LOD score of 6.82, at recombination fraction.041, for D12S1030. Candidate genes in this region include ATP2A2, ATP2B1, UBE3B, and VR-OAC. DFNA25 may be the human ortholog of bronx waltzer (bv).

Published
2001
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