Purchase this article with an account.
R. T. Libby, G. R. Howell, I. M. Cosma, L. A. Wilson, R. S. Smith, S. W. M. John; The Wallerian Degeneration Slow Protein Lessens Glaucomatous Damage in DBA/2J Mice. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2878.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Previously, we have shown that BAX deficiency protected retinal ganglion cell (RGC) somas but not their axons from degeneration in DBA/2J (D2) glaucoma. These data demonstrated that an axonal degeneration pathway is an important component of glaucomatous neurodegeneration and that it is molecularly distinct from somal apoptosis. The Wallerian degeneration slow (WldS) allele is a naturally occurring mutation that protects from direct axon injury. Here we use WldS to test the importance of axonal degeneration in D2 glaucoma.
WldS was backcrossed into the D2 strain. Intraocular pressure (IOP) measurement was performed at various ages to determine if WldS affected the IOP elevation of D2. The presence of WldS did not affect IOP. Optic nerves from 12 month old mice (an age where the majority of eyes have severe glaucoma) were determined to have different stages of glaucoma using an established grading scale.
The WldS transgene significantly lessened ON damage (p<0.001; following given as number mild, moderate, severe and total nerves: D2 7,2,30,39; D2.WldS 26,11,22,59). To determine if inhibiting apoptosis can enhance the protection of WldS, D2 mice that were WldS Bax+/- were analyzed. Bax heterozygosity significantly enhances the protection of WldS alone (P<0.05 compared to WldS alone; D2.WldS Bax+/- 38,14,11,63).
An axon-intrinsic degeneration pathway(s) is an important component of D2 glaucoma. WldS protects RGC axons from glaucomatous neurodegeneration, suggesting that the mechanisms by which WldS protects axons might be therapeutically exploited to treat glaucoma. Importantly, inhibiting RGC apoptosis enhanced the protection of WldS. Together, these data suggest the importance of both axonal and somal degeneration pathways in glaucoma.
This PDF is available to Subscribers Only