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

Publication ,  Journal Article
McKinnon, SJ; Lehman, DM; Tahzib, NG; Ransom, NL; Reitsamer, HA; Liston, P; LaCasse, E; Li, Q; Korneluk, RG; Hauswirth, WW
Published in: Mol Ther
June 2002

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.

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Published In

Mol Ther

DOI

ISSN

1525-0016

Publication Date

June 2002

Volume

5

Issue

6

Start / End Page

780 / 787

Location

United States

Related Subject Headings

  • X-Linked Inhibitor of Apoptosis Protein
  • Transgenes
  • Retinal Ganglion Cells
  • Rats
  • Proteins
  • Optic Nerve
  • Intraocular Pressure
  • Humans
  • Glaucoma
  • Genetic Vectors
 

Citation

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McKinnon, S. J., Lehman, D. M., Tahzib, N. G., Ransom, N. L., Reitsamer, H. A., Liston, P., … Hauswirth, W. W. (2002). Baculoviral IAP repeat-containing-4 protects optic nerve axons in a rat glaucoma model. Mol Ther, 5(6), 780–787. https://doi.org/10.1006/mthe.2002.0608
McKinnon, Stuart J., Donna M. Lehman, N Grace Tahzib, Nancy L. Ransom, Herbert A. Reitsamer, Peter Liston, Eric LaCasse, Qiuhong Li, Robert G. Korneluk, and William W. Hauswirth. “Baculoviral IAP repeat-containing-4 protects optic nerve axons in a rat glaucoma model.Mol Ther 5, no. 6 (June 2002): 780–87. https://doi.org/10.1006/mthe.2002.0608.
McKinnon SJ, Lehman DM, Tahzib NG, Ransom NL, Reitsamer HA, Liston P, et al. Baculoviral IAP repeat-containing-4 protects optic nerve axons in a rat glaucoma model. Mol Ther. 2002 Jun;5(6):780–7.
McKinnon, Stuart J., et al. “Baculoviral IAP repeat-containing-4 protects optic nerve axons in a rat glaucoma model.Mol Ther, vol. 5, no. 6, June 2002, pp. 780–87. Pubmed, doi:10.1006/mthe.2002.0608.
McKinnon SJ, Lehman DM, Tahzib NG, Ransom NL, Reitsamer HA, Liston P, LaCasse E, Li Q, Korneluk RG, Hauswirth WW. Baculoviral IAP repeat-containing-4 protects optic nerve axons in a rat glaucoma model. Mol Ther. 2002 Jun;5(6):780–787.
Journal cover image

Published In

Mol Ther

DOI

ISSN

1525-0016

Publication Date

June 2002

Volume

5

Issue

6

Start / End Page

780 / 787

Location

United States

Related Subject Headings

  • X-Linked Inhibitor of Apoptosis Protein
  • Transgenes
  • Retinal Ganglion Cells
  • Rats
  • Proteins
  • Optic Nerve
  • Intraocular Pressure
  • Humans
  • Glaucoma
  • Genetic Vectors