Abstract
Abstract: :
Purpose:. To assess functional neuroprotection from N-methyl-N-nitrosourea (MNU) induced retinal degeneration by XIAP, an X-linked inhibitor of apoptosis. Methods:At 6 weeks of age, thirty male Sprague-Dawley rats had a sub-retinal injection in one eye of adeno-associated virus encoding XIAP. At 6 weeks post-injection the animals received intra-peritoneal injection of 60 mg/kg of MNU, a DNA methylating agent. Flash electroretinograms (ERGs) were recorded from dark adapted eyes using DTL-fiber electrodes over an intensity range of –3.0 to 1.4 log cd.s/m2. ERGs were recorded at pre-treatment baseline and at 24, 48, 72 hours and 1 week post-MNU injection. Results:By 24 hours post-MNU injection the b-wave was significantly diminished in amplitude and delayed in both control and treated eyes (p<0.003); however, in 50% of animals the XIAP injected eye had significantly greater amplitude. By 1 week post-MNU injection the ERG was extinguished in all control eyes; whereas, an ERG was present in 33% of XIAP injected eyes. Conclusion:These results suggest that XIAP offers functional neuroprotection against this potent chemotoxic agent.
Keywords: 396 electroretinography: non-clinical • 419 gene transfer/gene therapy • 554 retina