Contact PD/PI: Park, Kevin (Kyung) Reconnection of Optic Nerve Poor regeneration of retinal ganglion cell (RGC) axons is a major obstacle for treating ocular trauma and optic neuropathies. There are as yet no therapies to repair optic nerve once the damage is done. Our past studies have demonstrated that simultaneous modulation of genes and neurotrophic factors promotes long distance regeneration of some RGCs in adult mice. However, promoting axons not only to regenerate into the lesion, but to travel long distances and reconnect their central targets is still a major challenge. In fact, we and others have reported various degrees of axon misguidance where few axons reinnervate brain targets while many others fail to do so. It is unclear what cellular and molecular factors contribute to the limited (or successful) pathfinding and target re-innervation. At present, very little is known about axon guidance mechanisms in adult mammalian visual system after injury. The overall goal of this proposal is to; i) establish an effective approach that promotes regeneration, reconnection of RGC axons and recovery of functions, ii) harness a new imaging technique (3Dtrace) to examine cell type-specific regeneration and reconnection, and iii) assess whether inactivating axon repulsive signaling improves target re-innervation. Identifying strategies to further increase regeneration and re-innervation in the brain represents critical future studies. Results obtained from these studies will provide invaluable information on developing future therapies to repair degenerated optic nerve after trauma or in diseases.

Public Health Relevance

Contact PD/PI: Park, Kevin (Kyung) Project Narrative Damage to retinal ganglion cell (RGC) axons is a major feature of glaucoma, optic neuritis and traumatic optic neuropathies. This grant will identify strategies that promote optimal regeneration and reconnection, and examine the mechanisms controlling axon guidance in the adult mammalian visual system.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY022961-06A1
Application #
9738406
Study Section
Diseases and Pathophysiology of the Visual System Study Section (DPVS)
Program Officer
Greenwell, Thomas
Project Start
2013-01-01
Project End
2020-09-29
Budget Start
2019-09-30
Budget End
2020-09-29
Support Year
6
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Miami School of Medicine
Department
Neurosurgery
Type
Schools of Medicine
DUNS #
052780918
City
Coral Gables
State
FL
Country
United States
Zip Code
33146
Fischer, Dietmar; Harvey, Alan R; Pernet, Vincent et al. (2017) Optic nerve regeneration in mammals: Regenerated or spared axons? Exp Neurol 296:83-88
Patel, Amit K; Park, Kevin K; Hackam, Abigail S (2017) Wnt signaling promotes axonal regeneration following optic nerve injury in the mouse. Neuroscience 343:372-383
Yungher, Benjamin J; Ribeiro, Márcio; Park, Kevin K (2017) Regenerative Responses and Axon Pathfinding of Retinal Ganglion Cells in Chronically Injured Mice. Invest Ophthalmol Vis Sci 58:1743-1750
Bray, Eric R; Noga, Markus; Thakor, Kinjal et al. (2017) 3D Visualization of Individual Regenerating Retinal Ganglion Cell Axons Reveals Surprisingly Complex Growth Paths. eNeuro 4:
Mehta, Saloni T; Luo, Xueting; Park, Kevin K et al. (2016) Hyperactivated Stat3 boosts axon regeneration in the CNS. Exp Neurol 280:115-20
Dvoriantchikova, Galina; Pappas, Steve; Luo, Xueting et al. (2016) Virally delivered, constitutively active NF?B improves survival of injured retinal ganglion cells. Eur J Neurosci 44:2935-2943
Luo, Xueting; Ribeiro, Marcio; Bray, Eric R et al. (2016) Enhanced Transcriptional Activity and Mitochondrial Localization of STAT3 Co-induce Axon Regrowth in the Adult Central Nervous System. Cell Rep 15:398-410
Soderblom, Cynthia; Lee, Do-Hun; Dawood, Abdul et al. (2015) 3D Imaging of Axons in Transparent Spinal Cords from Rodents and Nonhuman Primates eNeuro 2:
Yungher, B J; Luo, X; Salgueiro, Y et al. (2015) Viral vector-based improvement of optic nerve regeneration: characterization of individual axons' growth patterns and synaptogenesis in a visual target. Gene Ther 22:811-21
Luo, Xueting; Yungher, Benjamin; Park, Kevin K (2014) Application of tissue clearing and light sheet fluorescence microscopy to assess optic nerve regeneration in unsectioned tissues. Methods Mol Biol 1162:209-17

Showing the most recent 10 out of 12 publications