Acetylcholine (ACh) is a transmitter in the vertebrate retina that affects the response properties of many ganglion cells. Eight alpha and three beta subunits of neuronal nicotinic acetylcholine receptors (nAChRs) have been cloned, and antibodies have been raised against them. These subunits can combine to form a large number of nAChR subtypes, each characterized by a unique subunit composition and physiological and pharmacological profile.
The specific aims are based on the hypothesis that 1) different retinal cell types express different combinations of nAChR subtypes, and that 2) different nAChR subtypes serve different functional roles in the retina. 1. Antisera production: The production of antisera against synthetic peptides corresponding to unique sequences of chick and mammalian alpha and beta subunits will be continued. These will then be used for use in the studies described in Specific Aims 2, 3, and 5. 2. Characterization of the nAChR-expressing cells in the avian and mammalian retina: Antibodies and antisera against alpha and beta subunits will be used to determine the nAChR expression pattern in the chick, rat, and rabbit retina. nAChr-expressing cells will be identified based upon their content of neurotransmitters, enzymes, or other molecular markers as revealed by conventional double label studies. The spatial relationships between the dendrites of the nAChR-expressing cells and the processes of other neurons will be studied in the same fashion. 3. Determination of the subunit composition and abundance of retinal nAChR subtypes: Immune precipitation experiments using the same antibodies and antisera as above will be used to determine the subunit composition of chick and rabbit retinal nAChR and to quantify their relative abundance. 4. Characterization of subpopulations of cholinergic amacrine cells: The cholinergic amacrine cells of the rabbit retina comprise at least two subpopulations based upon nAChR and GABA expression. These subpopulations will be characterized in terms of their density, distribution, and the spatial relationships between the dendrites of these cells and those of other retinal neurons. 5. Cholinergic circuitry in the developing mammalian retina: Subunit specific antibodies and antisera will be used in conjunction with commercially available antisera to determine the pattern of choline acetyltransferase, GABA, and nAChR expression in retinas from postnatal ferrets of known ages.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY007845-11
Application #
6178982
Study Section
Visual Sciences C Study Section (VISC)
Program Officer
Hunter, Chyren
Project Start
1988-12-01
Project End
2003-09-29
Budget Start
2000-09-30
Budget End
2003-09-29
Support Year
11
Fiscal Year
2000
Total Cost
$264,634
Indirect Cost
Name
University of Alabama Birmingham
Department
Physiology
Type
Schools of Optometry/Ophthalmol
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Strang, Christianne E; Long, Ye; Gavrikov, Konstantin E et al. (2015) Nicotinic and muscarinic acetylcholine receptors shape ganglion cell response properties. J Neurophysiol 113:203-17
Varghese, Stefanie B; Reid, Jamie C; Hartmann, E Eugenie et al. (2011) The effects of nicotine on the human electroretinogram. Invest Ophthalmol Vis Sci 52:9445-51
Strang, Christianne E; Renna, Jordan M; Amthor, Franklin R et al. (2010) Muscarinic acetylcholine receptor localization and activation effects on ganglion response properties. Invest Ophthalmol Vis Sci 51:2778-89
Liu, Ji; McGlinn, Alice M; Fernandes, Alcides et al. (2009) Nicotinic acetylcholine receptor subunits in rhesus monkey retina. Invest Ophthalmol Vis Sci 50:1408-15
Cimini, Beth A; Strang, Christianne E; Wotring, Virginia E et al. (2008) Role of acetylcholine in nitric oxide production in the salamander retina. J Comp Neurol 507:1952-63
Dmitrieva, Nina A; Strang, Christianne E; Keyser, Kent T (2007) Expression of alpha 7 nicotinic acetylcholine receptors by bipolar, amacrine, and ganglion cells of the rabbit retina. J Histochem Cytochem 55:461-76
Siegwart Jr, John Thomas; Strang, Christianne E (2007) Selective modulation of scleral proteoglycan mRNA levels during minus lens compensation and recovery. Mol Vis 13:1878-86
Dmitriev, Andrey V; Dmitrieva, Nina A; Keyser, Kent T et al. (2007) Multiple functions of cation-chloride cotransporters in the fish retina. Vis Neurosci 24:635-45
Strang, Christianne E; Renna, Jordan M; Amthor, Franklin R et al. (2007) Nicotinic acetylcholine receptor expression by directionally selective ganglion cells. Vis Neurosci 24:523-33
Renna, J M; Strang, C E; Amthor, F R et al. (2007) Strychnine, but not PMBA, inhibits neuronal nicotinic acetylcholine receptors expressed by rabbit retinal ganglion cells. Vis Neurosci 24:503-11

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