Recent observations in neonatal rabbit retina reveal highly complex maturation patterns for neurotransmitter systems such as gamma amino butyric acid (GABA). The normal maturation process appears to involve the emergence of GABA related properties (i.e., uptake) in a variety of different neurons followed by selective elimination of these properties postnatally in all but a limited population of neurons which represent mature, GABAergic amacrine cells. The transient expression of GABAergic properties by horizontal cells associated with the outer plexiform layer (OPL) and by ganglion cells associated with the inner plexiform layer (IPL) raise the possibility that GABA may have a unique developmental function, in addition to its role as an important inhibitory neurotransmitter in the adult retina. This suggestion is supported in general by reports that GABA acts as a trophic agent in other neuronal systems. More specific circumstantial evidence is provided by the observations that 1) horizontal cells are the pioneer elements of the OPL, forming laterally arranged processes along which growing elements of the OPL accrue, and 2) horizontal cells express GABAergic properties at a time coincident with initiation of synaptogenesis in the OPL. The overall goal is to examine the developmental processess which are responsible for functional GABAergic circuits in the adult. We propose to investigate the possibility that a) GABA can be used as a marker for horizontal (and perhaps ganglion) cells which may perform trophic functions in the development of retinal plexiform layers; and/or b) GABA itself may function as a trophic substance. Light and electron microscopy and autoradiography will be used to analyze the development of the OPL and its relationship to the 3H-GABA accumulating horizontal cell. Other autoradiographic and immunocytochemical markers will be developed to aid in this analysis. The horizontal cell will be lesioned chemically and GABAergic processes blocked in order to determine if the anatomical or chemical integrity of the horizontal cell is necessary for normal postnatal development of the OPL. Postnatal development of the GABAergic cells in the inner retina will also be monitored in these experiments. Finally, the ability of GABA accumulating cell populations to release both endogenous and exogenously applied GABA will be examined during development. Expectations are to produce fundamental knowledge about the GABA neurotransmitter system in the vertebrate retina and its relationship to neuronal development.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY001655-11
Application #
3256084
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1983-03-01
Project End
1991-11-30
Budget Start
1987-12-01
Budget End
1988-11-30
Support Year
11
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Texas Health Science Center Houston
Department
Type
Schools of Medicine
DUNS #
City
Houston
State
TX
Country
United States
Zip Code
77225
Wei, Haiyang; Bonjean, Maxime; Petry, Heywood M et al. (2011) Thalamic burst firing propensity: a comparison of the dorsal lateral geniculate and pulvinar nuclei in the tree shrew. J Neurosci 31:17287-99
Wei, Haiyang; Masterson, Sean P; Petry, Heywood M et al. (2011) Diffuse and specific tectopulvinar terminals in the tree shrew: synapses, synapsins, and synaptic potentials. PLoS One 6:e23781
Johnson, Dianna A; Sharma, Rajesh K; Allan, Katherine et al. (2004) Immunocytochemical localization of polyamines during attachment and spreading of retinal pigment epithelial and intestinal epithelial cells. Cell Motil Cytoskeleton 58:269-80
Sharma, Rajesh K; O'Leary, T E; Fields, Carolyn M et al. (2003) Development of the outer retina in the mouse. Brain Res Dev Brain Res 145:93-105
Calzada, Jorge I; Jones, B Eric; Netland, Peter A et al. (2002) Glutamate-induced excitotoxicity in retina: neuroprotection with receptor antagonist, dextromethorphan, but not with calcium channel blockers. Neurochem Res 27:79-88
Johnson, Dianna A; Fields, Carolyn; Fallon, Amy et al. (2002) Polyamine-dependent migration of retinal pigment epithelial cells. Invest Ophthalmol Vis Sci 43:1228-33
Withrow, Catherine; Ashraf, Safeer; O'Leary, Timothy et al. (2002) Effect of polyamine depletion on cone photoreceptors of the developing rabbit retina. Invest Ophthalmol Vis Sci 43:3081-90
Sharma, R K (2001) Development and survival of tyrosine hydroxylase containing neurons in RCS rat retinae. Curr Eye Res 23:256-62
Withrow, C M; Johnson, D A (2001) Photoreceptor-horizontal cell reaggregation in monolayer cultures of neonatal rabbit retina. J Comp Neurol 431:241-54
Sharma, R K (2001) Bcl-2 expression during the development and degeneration of RCS rat retinae. Brain Res Dev Brain Res 132:81-6

Showing the most recent 10 out of 31 publications