The proposed research will study the role of the fibroblast growth factors (FGFS) on development and regeneration in the visual system. Blindness, whether caused by trauma, diabetic retinopathy, ischemic injury, tumors, infection, or other injury has a dramatic and permanent effect on the quality of an individuals life. The long term goals of this research are to improve knowledge about the factors involved in the development of the retina and its projections to the central nervous system and to develop methods of intervention that will optimize functional recovery of vision after injury. The proposed studies will explore the hypothesis that acidic and basic fibroblast growth factors (aFGF and bFGF), influence development and regeneration in the visual system. The rodent visual system has been chosen for study based on preliminary observations, and the feasibility of experimental manipulation. The FGFs have been isolated from retina and brain and have been shown to have a positive effect on process regeneration in retinal ganglion cells (RGC) in culture. There is also evidence that RGC viability can be increased by experimental manipulations (i,e. attaching a peripheral nerve graft to a severed optic nerve). The experiments in this proposal are specifically designed to: 1) localize aFGF & bFGF, aFGF & bFGF receptors and a &b FGF mRNA in the retina and primary CNS visual areas during development, 2) identify changes in localization and expression of AFGF & BFGF, AFGF & BFGF receptors and AFGF & BFGF MRNA following optic nerve injury, 3) study the effects of exogenous intraocular injection of the FGFs on RGC viability and regeneration following optic nerve injury, 4) study the effect of FGF filled nerve guides attached to severed optic nerve stump on RGC viability and regeneration.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Physician Scientist Award (K11)
Project #
5K11EY000311-05
Application #
3086813
Study Section
Vision Research and Training Committee (VSN)
Project Start
1991-08-01
Project End
1994-07-31
Budget Start
1993-08-01
Budget End
1994-07-31
Support Year
5
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115
Nakaya, Naoki; Lee, Hee-Sheung; Takada, Yuichiro et al. (2008) Zebrafish olfactomedin 1 regulates retinal axon elongation in vivo and is a modulator of Wnt signaling pathway. J Neurosci 28:7900-10
Lee, Hee-Sheung; Tomarev, Stanislav I (2007) Optimedin induces expression of N-cadherin and stimulates aggregation of NGF-stimulated PC12 cells. Exp Cell Res 313:98-108
Nakaya, Naoki; Tomarev, Stanislav (2007) Expression patterns of alternative transcripts of the zebrafish olfactomedin 1 genes. Gene Expr Patterns 7:723-9
Kostyk, S K; Wheeler, E L; Wagner, J A (1996) Unusual expression of the Hu paraneoplastic antigen in the visual system. Neuroreport 7:1549-52
Kostyk, S K; Kourembanas, S; Wheeler, E L et al. (1995) Basic fibroblast growth factor increases nitric oxide synthase production in bovine endothelial cells. Am J Physiol 269:H1583-9
Kostyk, S K; D'Amore, P A; Herman, I M et al. (1994) Optic nerve injury alters basic fibroblast growth factor localization in the retina and optic tract. J Neurosci 14:1441-9
McQuillan, L P; Leung, G K; Marsden, P A et al. (1994) Hypoxia inhibits expression of eNOS via transcriptional and posttranscriptional mechanisms. Am J Physiol 267:H1921-7
Smith, L E; Wesolowski, E; McLellan, A et al. (1994) Oxygen-induced retinopathy in the mouse. Invest Ophthalmol Vis Sci 35:101-11
Reidy, J J; McDonald, M B; Klyce, S D (1990) The corneal topography of epikeratophakia. Refract Corneal Surg 6:26-31