advertisement
Abstract #49168 Published in IGR 14-1
Glaucoma-Induced Degeneration of Retinal Ganglion Cells Prevented by Hypoxic Preconditioning: A Model of "Glaucoma Tolerance"
Zhu Y; Zhang L; Schmidt JF; Gidday JMMolecular Medicine 2012; 18: 697-706
Like all cells, neurons adapt to stress by transient alterations in phenotype, an epigenetic response that forms the basis for preconditioning against acute ischemic injury in the CNS. We recently showed that a modified repetitive hypoxic preconditioning regimen significantly extends the window of ischemic tolerance to acute retinal ischemic injury from days to months. The present study was undertaken to determine if this uniquely protracted neuroprotective phenotype would also confer resistance to glaucomatous neurodegeneration. Retinal ganglion cell death at somatic and axonal levels was assessed after both three and ten weeks of sustained intraocular hypertension in an adult mouse model of inducible, open-angle glaucoma, with or without repetitive hypoxic preconditioning (RHP) prior to IOP elevation. Loss of brn3-positive ganglion cell soma after 3 wks of experimental glaucoma, along with increases in several apoptotic endpoints, were all significantly and robustly attenuated in mice subjected to RHP. Soma protection by RHP was also confirmed after 10 wks of intraocular hypertension by brn3 and SMI32 immunostaining. In addition, quantification of axon density in postlaminar optic nerve documented robust preservation in RHP-treated mice, and neurofilament immunostaining also revealed preconditioning-induced improvements in axon integrity/survival in both retina and optic nerve after 10 wks of experimental glaucoma. This uniquely protracted period of phenotypic change, established in retinal ganglion cells by the activation of latent anti-apoptotic, pro-survival mechanisms at both somatic and axonal levels, reflects a novel form of inducible neuronal plasticity that may provide novel therapeutic targets for preventing and treating glaucoma and other neurodegenerative diseases.
Department of Neurosurgery, Washington University School of Medicine, St. Louis, MO, USA.
Full articleClassification:
5.1 Rodent (Part of: 5 Experimental glaucoma; animal models)
11.8 Neuroprotection (Part of: 11 Medical treatment)
