Potential synergistic protection of retinal ganglion cells from axotomy-induced apoptosis by adenoviral administration of glial cell line-derived neurotrophic factor and X-chromosome-linked inhibitor of apoptosis

Neurobiol Dis. 2002 Oct;11(1):123-33. doi: 10.1006/nbdi.2002.0543.


Following transection of the optic nerve (ON) in the adult rat, retinal ganglion cells (RGCs) undergo degeneration, and within 14 days 85% of axotomized RGCs die by apoptosis. Adenoviral delivery of the mammalian caspase inhibitor X-chromosome-linked inhibitor of apoptosis (Ad.XIAP) to the ON stump leads to expression exclusively in RGCs and rescues 18.9% of the RGCs that would degenerate without treatment. Following adenoviral vector injection into the vitreous body, bioactive glial cell line-derived neurotrophic factor (Ad.GDNF) is expressed in the retina and secreted to rescue 22.8% of lesioned RGCs. Here we report that coadministration of Ad.XIAP retrogradely directed to RGCs and intravitreal Ad.GDNF acts synergistically to protect axotomized RGCs. Combination treatment rescued 47.3% of RGCs that would undergo apoptosis without any treatment as opposed to 37.4% that would be expected if the two treatments acted independently. While without treatment only 15% of axotomized RGCs would survive, combination treatment resulted in survival of 55.4% of the total RGC population. These findings underline the neuroprotective potential of synergistic effects of a combination of different treatment strategies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Apoptosis*
  • Axotomy
  • Cell Survival
  • Female
  • Gene Expression
  • Genetic Therapy*
  • Glial Cell Line-Derived Neurotrophic Factor
  • Nerve Degeneration / pathology
  • Nerve Degeneration / prevention & control
  • Nerve Degeneration / therapy
  • Nerve Growth Factors / genetics*
  • Neuroprotective Agents
  • Proteins / genetics*
  • Rats
  • Rats, Sprague-Dawley
  • Retinal Ganglion Cells / pathology
  • Retinal Ganglion Cells / physiology*
  • X-Linked Inhibitor of Apoptosis Protein


  • Gdnf protein, rat
  • Glial Cell Line-Derived Neurotrophic Factor
  • Nerve Growth Factors
  • Neuroprotective Agents
  • Proteins
  • X-Linked Inhibitor of Apoptosis Protein