Leonard A. Levin

 

 

Mechanisms of Axotomy-Induced Apoptosis

Research Strength: Neurobiology of Disease

My main research interest is to better understand the subcellular events underlying death of retinal ganglion cells due to axonal injury. These cells are identified central neurons which have anatomically separated axons, allowing dissection of the neuronal responses to axonal damage. Our working hypothesis is that axotomy of retinal ganglion cells causes expression of genes that turn on a program for cell death involving reactive oxygen species and opening of the mitochondrial permeability transition pore, and that these genes and their products can be characterized, and eventually modulated. We also study the role of these and other genes in primary retinal cultures. We can then examine the initiating steps in neuronal death, and ways to inhibit them. Since certain clinical syndromes (glaucoma, multiple sclerosis, etc.) cause blindness via optic nerve injury; this research may eventually be applicable to human disease.

Selected Publications:

• Lieven, C.J., L.E. Millet, L.A. Levin. Induction of axon and dendrite formation during early RGC-5 cell differentiation. Exp Eye Res, in press.
• Nguyen, S.M., C.J. Lieven, L.A. Levin. 2007. Simultaneous labeling of projecting neurons and apoptotic state, J Neurosci Methods 161:281-284.
• Schwechter, B.R., L.E. Millet, L.A. Levin. 2007. Histone deacetylase inhibition-mediated differentiation of RGC-5 cells and interaction with survival. Invest Ophthalmol Vis Sci 48:2845-2857. [PDF]
• Frassetto, L.J., C.R. Schlieve, A.A. Utter, M.V. Jones, N. Agarwal, L.A. Levin. 2006. Kinase-dependent differentiation of a retinal ganglion cell precursor. Invest Ophthalmol Vis Sci, 47:427-438. [PDF]
• Lieven, C.J., M.J. Hoegger, C.R. Schlieve, L.A. Levin. 2006. Retinal ganglion cell axotomy induces an increase in intracellular superoxide anion. Invest Ophthalmol Vis Sci, 47:1477-1485. [PDF]
• Schlieve, C.R., C.J. Lieven, L.A. Levin. 2006. Biochemical activity of reactive oxygen species scavengers do not predict retinal ganglion cell survival. Invest Ophthalmol Vis Sci, 47:3878-86. [PDF]
• Schlieve, C.R., A. Tam, B.L. Nilsson, C.J. Lieven, R.T. Raines, L.A. Levin. Synthesis and characterization of a novel class of reducing agents that are highly neuroprotective for retinal ganglion cells. Exp Eye Res, 83:1252-1259, 2006. [PDF]
• Conley, L., T.L. Geurs, and L.A. Levin. 2005. Transcriptional regulation of ceruloplasmin by an IL-6 response element pathway. Mol. Brain Res. 139: 235-241.
• Swanson, K.I., C.R. Schlieve, C.J. Lieven, L.A. Levin. 2005. Neuroprotective effect of sulfhydryl reduction in a rat optic nerve crush model. Invest. Ophthalmol. Vis. Sci. 46: 3737-3741.
• Vrabec, J.P., C.J. Lieven, and L.A. Levin. 2003. Cell type specific opening of the retinal ganglion cell mitochondrial permeability transition pore, Invest. Ophthalmol. Vis. Sci. 44: 2774-2782. [PDF]
• Lieven, C.J., J.P. Vrabec, and L.A. Levin. 2003. The effects of oxidative stress on mitochondrial transmembrane potential in retinal ganglion cells. Antioxid. Redox. Signal 5: 641-646/.
• Schmehil, A.L. and L.A. Levin. 2003. Transient transfection protects PC6-3 cells from apoptosis induced by NGF deprivation. Neuroscience 116: 23-29. [PDF]
• Geiger, L.K., K.R. Kortuem, C. Alexejun, and L.A. Levin. 2002. Reduced redox state allows prolonged survival of axotomized neonatal retinal ganglion cells. Neuroscience 109: 635-642. [PDF]
• Kortuem, K.R., L.K. Geiger, and L.A. Levin. 2000. Differential susceptibility of retinal ganglion cells to reactive oxygen species. Invest. Ophthalmol. Vis. Sci. 41: 3176-3182. [PDF]