The long-term goal of this research is to understand how peptidergic neurons contribute to information processing in the primate retina. Retinal peptides were previously thought to act primarily as neuromodulators, and the localizations of immunoreactive peptides in wide-field amacrine, associational and interplexiform cells that made the majority of their contacts with amacrine cells seemed to support this hypothesis. During the first grant period, however, some peptidergic amacrine were found to make extensive contacts with bipolar and ganglion cells. The most striking exception to the earlier generalizations about peptide function was the localization of a peptide to a type of bipolar cell. These results in the first grant period suggested that peptidergic cells are not only interacting with the most direct pathway for visual information; they also appear to be used as neurotransmitters by the cells that comprise that pathway. In the experiments proposed in this application for renewal, the emphasis will shift from the peptides, themselves, to the functions of the cells that contain them. Light microscopic double label experiments will be designed to identify the full complement of chemical messengers in each type of cell. Based on those results, electron microscopic double label experiments will be designed to identify the cells contacted by the peptidergic neurons, and other neurons in the circuits will be identified by serial reconstruction of electron micrographs. Studies with cryofixed retina will determine whether peptides are stored in and, presumably, released from synaptic vesicles. The light microscopic techniques developed for the macaque monkey retina will also be applied to the human retina, and the results would provide the basis for studies of peptidergic neurons in diseased eyes. Recent studies showing changes in retinal peptide levels after experimentally induced diabetes suggest that these neurons may be selectively affected by retinal diseases. The proposed experiments with peptidergic bipolar cells are particularly likely to have clinical relevance since they appear to contact the short wavelength cones. The short wavelength system is particularly vulnerable in the early stages of a number of retinal diseases, and the proposed basic research on the synaptic interactions in that pathway might facilitate the interpretation of the deficits.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY006472-06
Application #
3262652
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1986-05-01
Project End
1994-09-29
Budget Start
1992-09-30
Budget End
1994-09-29
Support Year
6
Fiscal Year
1992
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
Bordt, Andrea S; Long, Ye; Kouyama, Nobuo et al. (2017) Wavy multistratified amacrine cells in the monkey retina contain immunoreactive secretoneurin. Peptides 94:33-42
Marshak, David W (2016) A tale of two neurotransmitters. Vis Neurosci 33:E017
Long, Ye; Bordt, Andrea S; Liu, Weiley S et al. (2016) Wide-field diffuse amacrine cells in the monkey retina contain immunoreactive Cocaine- and Amphetamine-Regulated Transcript (CART). Peptides 84:22-35
Marshak, David W; Chuang, Alice Z; Dolino, Drew M et al. (2015) Synaptic connections of amacrine cells containing vesicular glutamate transporter 3 in baboon retinas. Vis Neurosci 32:E006
Marshak, David W; Mills, Stephen L (2014) Short-wavelength cone-opponent retinal ganglion cells in mammals. Vis Neurosci 31:165-75
Vila, Alejandro; Satoh, Hiromasa; Rangel, Carolina et al. (2012) Histamine receptors of cones and horizontal cells in Old World monkey retinas. J Comp Neurol 520:528-43
Yu, Yongchun; Satoh, Hiromasa; Vila, Alejandro et al. (2011) Effects of histamine on light responses of amacrine cells in tiger salamander retina. Neurochem Res 36:645-54
Frazao, Renata; McMahon, Douglas G; Schunack, Walter et al. (2011) Histamine elevates free intracellular calcium in mouse retinal dopaminergic cells via H1-receptors. Invest Ophthalmol Vis Sci 52:3083-8
Akimov, Nikolay P; Marshak, David W; Frishman, Laura J et al. (2010) Histamine reduces flash sensitivity of on ganglion cells in the primate retina. Invest Ophthalmol Vis Sci 51:3825-34
Klump, Kathryn E; Zhang, Ai-Jun; Wu, Samuel M et al. (2009) Parvalbumin-immunoreactive amacrine cells of macaque retina. Vis Neurosci 26:287-96

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