Local administration of an adeno-associated viral vector expressing IL-10 reduces monocyte infiltration and subsequent photoreceptor damage during experimental autoimmune uveitis.
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.
Broderick
Cathryn A
CA
Division of Molecular Therapy, Institute of Ophthalmology, University College, London, 11-43 Bath Street, London EC1V 9EL, UK.
Smith
Alexander J
AJ
Balaggan
Kam S
KS
Georgiadis
Anastasios
A
Georgarias
Anastasios
A
Buch
Prateek K
PK
Trittibach
Peter C
PC
Barker
Susie E
SE
Sarra
Gian-Marco
GM
Thrasher
Adrian J
AJ
Dick
Andrew D
AD
Ali
Robin R
RR
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy*; D000229:Dependovirus / Q000235:genetics*; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000627:therapeutic use; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000187:drug effects / Q000502:physiology; D020419:Photoreceptor Cells, Vertebrate / Q000276:immunology*; D012162:Retinal Degeneration; D014605:Uveitis / Q000276:immunology / Q000628:therapy*
D016753:Interleukin-10