Establishment of the specific cell-cell interactions required in nervous systems almost certainly requires the participation of unique cell surface and extracellular matrix components. The ability of neuronal cells to distinguish themselves from others, migrate to specific sites, and elaborate ordered functional connections is likely to depend upon interactions among complex arrays of cell membrane-associated molecules. The expression of specific surface constituents may thus establish the identity of individual neuronal cell types and function in the development and maintenance of specific intercellular interactions. Our primary recent interest has been in glycoconjugate molecules specifically associated with cone, as opposed to rod, photoreceptor cells in the neural retina. This interest was spurred by the observation that the lectin peanut agglutinin (PNA) binds specifically to cones in a variety of vertebrate retinae. We have begun the characterization of retinal molecules bound by PNA and have prepared cone-specific immunologic probes. In the proposed studies we wish to characterize further the biochemistry of molecules expressed by cone photoreceptors and examine possible roles for such molecules in the development, differentiation, and function of the retina. Retinal molecules bound by cone-specific antibodies will be characterized biochemically, their ultrastructural localization determined immunocytochemically, and their cross reactivity with retinae in a variety of species as well as with other neural and non-neural tissues will be assessed. The expression of cone-specific molecules during retinal development and in association with hereditary retinal degeneration will also be monitored. The biochemical characteristics of cone-specific domains in the interphotoreceptor matrix and their cellular source of will be investigated. Finally, the differentiation-dependent expression of glycoconjugate molecules by retinoblastoma cells in vitro will be monitored with the intent to relate such molecular changes to differentiative events in the developing retina and tumorigenicity of retinoblastoma cells.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY004741-08
Application #
3259208
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1983-04-01
Project End
1992-03-31
Budget Start
1990-04-01
Budget End
1992-03-31
Support Year
8
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Southern California
Department
Type
Schools of Medicine
DUNS #
041544081
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Tombran-Tink, J; Shivaram, S M; Chader, G J et al. (1995) Expression, secretion, and age-related downregulation of pigment epithelium-derived factor, a serpin with neurotrophic activity. J Neurosci 15:4992-5003
Hageman, G S; Marmor, M F; Yao, X Y et al. (1995) The interphotoreceptor matrix mediates primate retinal adhesion. Arch Ophthalmol 113:655-60
Blanks, J C; Johnson, L V; Hageman, G S (1993) Stage-specific binding of peanut agglutinin to aggregates of degenerating photoreceptor cells in the rd mouse retina. Exp Eye Res 57:265-73
Johnson, L V; Hageman, G S (1991) Structural and compositional analyses of isolated cone matrix sheaths. Invest Ophthalmol Vis Sci 32:1951-7
Tombran-Tink, J; Johnson, L V (1989) Neuronal differentiation of retinoblastoma cells induced by medium conditioned by human RPE cells. Invest Ophthalmol Vis Sci 30:1700-7
Johnson, L V; Blanks, J C; Hageman, G S (1989) Effects of retinal degenerations on the cone matrix sheath. Prog Clin Biol Res 314:217-32
Tombran-Tink, J; Johnson, L V (1989) Collagen-induced alterations in intercellular adhesion and antigen expression in retinoblastoma cells. Exp Eye Res 48:549-59
Blanks, J C; Hageman, G S; Johnson, L V et al. (1988) Ultrastructural visualization of primate cone photoreceptor matrix sheaths. J Comp Neurol 270:288-300
Johnson, L V; Hageman, G S (1988) Characterization of molecules bound by the cone photoreceptor-specific monoclonal antibody CSA-1. Invest Ophthalmol Vis Sci 29:550-7
Hageman, G S; Johnson, L V (1987) Chondroitin 6-sulfate glycosaminoglycan is a major constituent of primate cone photoreceptor matrix sheaths. Curr Eye Res 6:639-46

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