The long-term objective of the proposed research is to understand the cellular mechanisms that underlie vision. The premise underlying this application is that the remarkable adaptability of vision is based on the plasticity of intracellular signaling pathways in retinal neurons. The focus of the work will be to study the mechanisms that regulate the intracellular Ca2+ concentration and transmitter release in retinal rod and cone photoreceptor neurons. The proposed experiments combine electrophysiological, optical and immunocytochemical methods. Results obtained in these studies will help us select cellular targets for therapeutic interventions during retinal disease and blindness.
Three specific aims are proposed: (1) to characterize Ca2+ regulation in photoreceptor inner segments; (2) to identify differences in Ca2+ homeostasis between rod and cone photoreceptor inner segments; and (3) to determine the relationship between [Ca2+]і and exocytosis in photoreceptors.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY013870-03
Application #
6706974
Study Section
Visual Sciences C Study Section (VISC)
Program Officer
Mariani, Andrew P
Project Start
2002-03-01
Project End
2006-02-28
Budget Start
2004-02-29
Budget End
2005-02-28
Support Year
3
Fiscal Year
2004
Total Cost
$227,250
Indirect Cost
Name
University of California San Francisco
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Butler, Michael R; Ma, Hongwei; Yang, Fan et al. (2017) Endoplasmic reticulum (ER) Ca2+-channel activity contributes to ER stress and cone death in cyclic nucleotide-gated channel deficiency. J Biol Chem 292:11189-11205
Križaj, David (2016) Polymodal Sensory Integration in Retinal Ganglion Cells. Adv Exp Med Biol 854:693-8
Molnár, Tünde; Yarishkin, Oleg; Iuso, Anthony et al. (2016) Store-Operated Calcium Entry in Müller Glia Is Controlled by Synergistic Activation of TRPC and Orai Channels. J Neurosci 36:3184-98
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Phuong, Tam T T; Yarishkin, Oleg; Križaj, David (2016) Subcellular propagation of calcium waves in Müller glia does not require autocrine/paracrine purinergic signaling. Channels (Austin) 10:421-427
Ryskamp, Daniel A; Iuso, Anthony; Križaj, David (2015) TRPV4 links inflammatory signaling and neuroglial swelling. Channels (Austin) 9:70-2
Cahoon, Judd M; Rai, Ruju R; Carroll, Lara S et al. (2015) Intravitreal AAV2.COMP-Ang1 Prevents Neurovascular Degeneration in a Murine Model of Diabetic Retinopathy. Diabetes 64:4247-59
Ryskamp, Daniel A; Redmon, Sarah; Jo, Andrew O et al. (2014) TRPV1 and Endocannabinoids: Emerging Molecular Signals that Modulate Mammalian Vision. Cells 3:914-38
Chen, Minghui; Križaj, David; Thoreson, Wallace B (2014) Intracellular calcium stores drive slow non-ribbon vesicle release from rod photoreceptors. Front Cell Neurosci 8:20
Križaj, David; Ryskamp, Daniel A; Tian, Ning et al. (2014) From mechanosensitivity to inflammatory responses: new players in the pathology of glaucoma. Curr Eye Res 39:105-19

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