In this competing renewal application, we propose to continue and extend our investigations on rod and cone signaling pathways at the bipolar cell (BC), amacrine cell (AC) and ganglion cell (GC) levels in the dark-adapted mouse retina. We will focus our efforts to study the BC and AC synaptic circuitries mediating rod, M-cone and M/S-cone signal transmission to three types of alpha ganglion cells (alphaGCs), and to determine how glycinergic and GABAergic ACs regulate light-evoked signals in alphaGCs via the AC cone BC GC feedback pathways and the AC GC feedforward synapses. There are three specific aims: (1) to correlate physiological BC types with anatomical BC types in the three alphaGC circuitries and to identify possible synaptic contacts between rods/cones and BCs and between BCs and alphaGCs;(2) to determine the relative strengths of rod- and cone-mediated inputs to BCs and alphaGCs and mechanisms of signal integration in the 3 alphaGC circuitries by analyzing BCs'and alphaGCs'light-evoked cation currents ( IC) in wildtype, Tralpha-/- and Gnat2cplf3 mice;and (3) to determine relative glycinergic and GABAergic AC contributions to alphaGCs'light-evoked inhibitory and BC synaptic inputs and possible synaptic connectivity between individual GABAergic ACs and alphaGCs by double label and dual voltage clamp techniques. The goal of our research is to understand how mammalian retinal networks process visual images, a basic research priority of the NEI, and to provide crucial information on how individual retinal neurons and synapses dysfunction in disease states, such as congenital stationary night blindness and glaucoma, a translational research priority of the NEI. Moreover, knowledge of specific mammalian retinal circuitries in healthy and diseased eyes will be useful for developing new gene/drug therapies for retinal disorders, such as retinitis pigmentosa and glaucoma, as well as for designing effective retinal prosthetic devices.

Public Health Relevance

The goal of our research is to understand how the mammalian retinal network processes visual information, and how individual retinal neurons and synapses dysfunction in eye diseases, such as retinitis pigmentosa, congenital stationary night blindness and glaucoma. Results obtained will provide a crucial knowledge base for developing new gene/drug therapies against retinal disorders and effective retinal prosthetic devices.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY019908-04A1
Application #
8573191
Study Section
Neurotransporters, Receptors, and Calcium Signaling Study Section (NTRC)
Program Officer
Greenwell, Thomas
Project Start
2010-01-01
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
4
Fiscal Year
2013
Total Cost
$391,250
Indirect Cost
$141,250
Name
Baylor College of Medicine
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
Cowan, Cameron S; Abd-El-Barr, Muhammad; van der Heijden, Meike et al. (2016) Connexin 36 and rod bipolar cell independent rod pathways drive retinal ganglion cells and optokinetic reflexes. Vision Res 119:99-109
He, Feng; Agosto, Melina A; Anastassov, Ivan A et al. (2016) Phosphatidylinositol-3-phosphate is light-regulated and essential for survival in retinal rods. Sci Rep 6:26978
Cowan, Cameron S; Sabharwal, Jasdeep; Wu, Samuel M (2016) Space-time codependence of retinal ganglion cells can be explained by novel and separable components of their receptive fields. Physiol Rep 4:
Wang, Jing; Jacoby, Roy; Wu, Samuel M (2016) Physiological and morphological characterization of ganglion cells in the salamander retina. Vision Res 119:60-72
van der Heijden, Meike E; Shah, Priya; Cowan, Cameron S et al. (2016) Effects of Chronic and Acute Intraocular Pressure Elevation on Scotopic and Photopic Contrast Sensitivity in Mice. Invest Ophthalmol Vis Sci 57:3077-87
Khan, A Kareem; Tse, Dennis Y; van der Heijden, Meike E et al. (2015) Prolonged elevation of intraocular pressure results in retinal ganglion cell loss and abnormal retinal function in mice. Exp Eye Res 130:29-37
Eblimit, Aiden; Nguyen, Thanh-Minh T; Chen, Yiyun et al. (2015) Spata7 is a retinal ciliopathy gene critical for correct RPGRIP1 localization and protein trafficking in the retina. Hum Mol Genet 24:1584-601
Pang, Ji-Jie; Frankfort, Benjamin J; Gross, Ronald L et al. (2015) Elevated intraocular pressure decreases response sensitivity of inner retinal neurons in experimental glaucoma mice. Proc Natl Acad Sci U S A 112:2593-8
Xiong, Wei-Hong; Pang, Ji-Jie; Pennesi, Mark E et al. (2015) The Effect of PKCα on the Light Response of Rod Bipolar Cells in the Mouse Retina. Invest Ophthalmol Vis Sci 56:4961-74
Tse, Dennis Y; Lotfi, Parisa; Simons, David L et al. (2015) Electrophysiological and Histological Characterization of Rod-Cone Retinal Degeneration and Microglia Activation in a Mouse Model of Mucopolysaccharidosis Type IIIB. Sci Rep 5:17143

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