The vertebrate retina is the primary visual organ. Visual information collected by the retinal ganglion neurons is transmitted to the brain via axons which make up the myelinated optic nerve. This nerve, besides being of key importance in vision, also serves as an excellent system to investigate axonal transport of membranous organelles and precursors of plasma membranes and synaptic vesicles. It has recently been shown that the severed optic nerve can, at least in part, regenerate along a peripheral nerve graft and reach the correct region of the brain, thus serving as an excellent system to examine the requirements for CNS regeneration. Finally, there is evidence of optic nerve pathology in Alzheimer's disease. For several years we have been investigating the rapid axonal transport machinery in rabbit, and more recently in bovine optic nerve. We have very recently characterized a group of low molecular weight GTP binding proteins associated with optic nerve rapid transport vesicles and potential target membranes, i.e. synaptic plasma membrane and synaptic vesicles. In view of the recent evidences defining an important role of this protein class in secretion and vesicular transport, we have proposed a systematic investigation of the structure, biosynthesis, localization and function of these low molecular weight GTP binding proteins. We will particularly localize these proteins in the developing retina and optic nerve. We will employ methods of biochemistry, tissue culture, immunocytochemistry and video intensification microscopy in these investigations. We feel that these studies will, hopefully, shed new light on the mechanism of rapid axonal transport in adult and developing optic nerve which may have significant implications for CNS development and potentially, regeneration.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY008535-02
Application #
3265887
Study Section
Visual Sciences B Study Section (VISB)
Project Start
1990-05-01
Project End
1995-04-30
Budget Start
1991-05-01
Budget End
1992-04-30
Support Year
2
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Boston University
Department
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Dunn, K C; Marmorstein, A D; Bonilha, V L et al. (1998) Use of the ARPE-19 cell line as a model of RPE polarity: basolateral secretion of FGF5. Invest Ophthalmol Vis Sci 39:2744-9
Shanmugaratnam, J; Berg, E; Kimerer, L et al. (1997) Retinal Muller glia secrete apolipoproteins E and J which are efficiently assembled into lipoprotein particles. Brain Res Mol Brain Res 50:113-20
Amaratunga, A; Abraham, C R; Edwards, R B et al. (1996) Apolipoprotein E is synthesized in the retina by Muller glial cells, secreted into the vitreous, and rapidly transported into the optic nerve by retinal ganglion cells. J Biol Chem 271:5628-32
Amaratunga, A; Fine, R E (1995) Generation of amyloidogenic C-terminal fragments during rapid axonal transport in vivo of beta-amyloid precursor protein in the optic nerve. J Biol Chem 270:17268-72
Amaratunga, A; Leeman, S E; Kosik, K S et al. (1995) Inhibition of kinesin synthesis in vivo inhibits the rapid transport of representative proteins for three transport vesicle classes into the axon. J Neurochem 64:2374-6
Amaratunga, A; Morin, P J; Kosik, K S et al. (1993) Inhibition of kinesin synthesis and rapid anterograde axonal transport in vivo by an antisense oligonucleotide. J Biol Chem 268:17427-30
Bielinski, D F; Pyun, H Y; Linko-Stentz, K et al. (1993) Ral and Rab3a are major GTP-binding proteins of axonal rapid transport and synaptic vesicles and do not redistribute following depolarization stimulated synaptosomal exocytosis. Biochim Biophys Acta 1151:246-56
Morin, P J; Johnson, R J; Fine, R E (1993) Kinesin is rapidly transported in the optic nerve as a membrane associated protein. Biochim Biophys Acta 1146:275-81
Morin, P J; Abraham, C R; Amaratunga, A et al. (1993) Amyloid precursor protein is synthesized by retinal ganglion cells, rapidly transported to the optic nerve plasma membrane and nerve terminals, and metabolized. J Neurochem 61:464-73