In adult mammals, severed optic axons, like most long projecting CNS axons, do not normally regenerate with the CNS so that axonal damage such as following spinal cord injury results in permanent deficits. However, it has recently been shown that optic fibers will regenerate when retina is placed in culture and that this regeneration is dramatically accelerated by prior optic nerve damage (Meyer & Miotke, 1987). This proposal will use such retinal explants from adult mice as a model to study the regenerative response of retinal fibers and to investigate cellular interactions and other factors that may be responsible for the lack of regeneration in the CNS. There are three major aims. The first is to optimize the culture conditions. Different gas mixtures, media, serum concentrations, additives, and methods of maintaining the explants will be explored. In addition, an attempt will be made to develop serum free culture conditions.
The second aim will be to further characterize the regenerative response. The number of ganglion cells that survive at short and long culture periods will be counted. The effect of the time and position of the nerve injury prior to explanation will be explored. Elongation rate and growth distance will be measured for early and late explants. And the effect of explant size and shape will be explored.
The third aim i s to confront growing optic neurites with several conditions that may be relevant to their environment. These include pieces of optic nerve from adults or neonates, pieces of sciatic nerve and different substrates of extracellular matrix including laminin, collagen, and fibronectin.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS026750-02
Application #
3412752
Study Section
Visual Sciences B Study Section (VISB)
Project Start
1988-12-01
Project End
1991-11-30
Budget Start
1989-12-01
Budget End
1990-11-30
Support Year
2
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of California Irvine
Department
Type
Schools of Arts and Sciences
DUNS #
161202122
City
Irvine
State
CA
Country
United States
Zip Code
92697
Miotke, Jill A; MacLennan, A John; Meyer, Ronald L (2007) Immunohistochemical localization of CNTFRalpha in adult mouse retina and optic nerve following intraorbital nerve crush: evidence for the axonal loss of a trophic factor receptor after injury. J Comp Neurol 500:384-400
Becker, C G; Becker, T; Meyer, R L (2001) Increased NCAM-180 immunoreactivity and maintenance of L1 immunoreactivity in injured optic fibers of adult mice. Exp Neurol 169:438-48
Becker, T; Anliker, B; Becker, C G et al. (2000) Tenascin-R inhibits regrowth of optic fibers in vitro and persists in the optic nerve of mice after injury. Glia 29:330-46
Becker, C G; Becker, T; Meyer, R L et al. (1999) Tenascin-R inhibits the growth of optic fibers in vitro but is rapidly eliminated during nerve regeneration in the salamander Pleurodeles waltl. J Neurosci 19:813-27
Bates, C A; Becker, C G; Miotke, J A et al. (1999) Expression of polysialylated NCAM but not L1 or N-cadherin by regenerating adult mouse optic fibers in vitro. Exp Neurol 155:128-39
Bates, C A; Meyer, R L (1997) The neurite-promoting effect of laminin is mediated by different mechanisms in embryonic and adult regenerating mouse optic axons in vitro. Dev Biol 181:91-101
Bates, C A; Meyer, R L (1996) Heterotrimeric G protein activation rapidly inhibits outgrowth of optic axons from adult and embryonic mouse, and goldfish retinal explants. Brain Res 714:65-75
Bates, C A; Meyer, R L (1994) Differential effect of serum on laminin-dependent outgrowth of embryonic and adult mouse optic axons in vitro. Exp Neurol 125:99-105
Meyer, R L; Miotke, J A; Benowitz, L I (1994) Injury induced expression of growth-associated protein-43 in adult mouse retinal ganglion cells in vitro. Neuroscience 63:591-602
Bates, C A; Trinh, N; Meyer, R L (1993) Distribution of microtubule-associated proteins (MAPs) in adult and embryonic mouse retinal explants: presence of the embryonic map, MAP5/1B, in regenerating adult retinal axons. Dev Biol 155:533-44

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