Baculoviral IAP repeat-containing-4 protects optic nerve axons in a rat glaucoma model.

Journal Article (Journal Article)

Gene therapy represents an attractive approach for the treatment of eye diseases such as glaucoma. Ocular administration of viral vectors produces localized retinal gene expression with reduced risks of side effects reported with systemic administration of viral vectors. Recombinant adeno-associated viral (AAV) vectors have proven effective in producing long-term retinal gene expression, due to stable integration of DNA into the genome and lack of host immune response to the virus. Recently developed AAV constructs using the chicken beta-actin (CBA) promoter drive highly efficient transgene expression in retinal ganglion cells (RGCs), photoreceptors, and pigment epithelium. Rats were given unilateral intravitreal injections of AAV-CBA vector coding for human baculoviral IAP repeat-containing protein-4 (BIRC4), a potent caspase inhibitor. Ocular hypertension was induced in the same eye by sclerosis of aqueous humor outflow channels. After chronic exposure to elevated intraocular pressure, we performed optic nerve axon counts to determine the neuroprotective effects of retinal BIRC4 expression, and compared axon survival with vector and balanced salt solution control groups. Gene therapy delivering BIRC4 significantly promoted optic nerve axon survival in a chronic ocular hypertensive model of rat glaucoma. Blocking RGC apoptosis with caspase inhibitors represents a promising approach for treatment of human glaucoma.

Full Text

Duke Authors

Cited Authors

  • McKinnon, SJ; Lehman, DM; Tahzib, NG; Ransom, NL; Reitsamer, HA; Liston, P; LaCasse, E; Li, Q; Korneluk, RG; Hauswirth, WW

Published Date

  • June 2002

Published In

Volume / Issue

  • 5 / 6

Start / End Page

  • 780 - 787

PubMed ID

  • 12027563

International Standard Serial Number (ISSN)

  • 1525-0016

Digital Object Identifier (DOI)

  • 10.1006/mthe.2002.0608


  • eng

Conference Location

  • United States