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

Stuart J. McKinnon, Donna M. Lehman, N. Grace Tahzib, Nancy L. Ransom, Herbert A. Reitsamer, Peter Liston, Eric LaCasse, Qiuhong Li, Robert G. Korneluk, William W. Hauswirth

Research output: Contribution to journalArticlepeer-review

130 Scopus citations


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 β-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.

Original languageEnglish (US)
Pages (from-to)780-787
Number of pages8
JournalMolecular Therapy
Issue number6
StatePublished - 2002


  • Adeno-associated virus
  • Animal
  • Apoptosis
  • Caspases
  • Gene therapy
  • Glaucoma
  • Intraocular pressure
  • Models
  • Ocular hypertension
  • Rats
  • Retinal ganglion cells
  • X-linked IAP

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery


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