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Calcium channels in retinal photoreceptors

Award Number: R01EY026817
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2017
PERIOD OF PERFORMANCE END DATE: 04/30/2026

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Calcium channels in retinal photoreceptors - The long-term goal of our research is to understand how the properties of Cav channels shape their neural functions. The objective of this competing renewal application is to define the Cav1-dependent signaling pathways that shape the development and plasticity of the photoreceptor (PR) synapse. Among the major Cav1 subtypes expressed in the retina, Cav1.4 is uniquely critical for PR synaptogenesis. How Cav1.4 contributes to this process remains a mystery—a major challenge being that available animal models do not distinguish between the roles of Cav1.4 as a source of Ca2+ ions and as a scaffold for synaptogenic proteins. To overcome this hurdle, we generated a knock-in mouse strain expressing a non-conducting mutant form of Cav1.4. While the molecular organization of PR synapses is largely spared in these mice, the maturation of synaptic ribbons and invagination of postsynaptic neurites into PR terminals is disrupted. Our findings raise the intriguing possibility that the clinical variability associated with CSNB2 could arise from heterogeneous impacts of the mutations on the organization, development, and mature function of the PR synapse. Our central hypothesis is that Cav1.4 mediates Ca2+ signaling pathways that promote the maturation of synaptic ribbons and the postsynaptic architecture of PR synapses via mechanisms that are disrupted in CSNB2. We will test this hypothesis with the following Aims: (1) Elucidate the mechanism whereby Cav1.4 Ca2+ signals regulate the maturation and plasticity of synaptic ribbons (2) Define the role of Cav1 Ca2+ signals in enabling the postsynaptic wiring of PR synapses (3) Determine the impact of pathological variants of human Cav1.4 channels on PR synapse structure and function. The overall impact of our research will be knowledge of: (a) the multi-faceted roles of Cav channels at a synapse that is crucial for vision, and (b) how dysregulation specifically of Cav1.4 could lead to heterogeneous forms of vision impairment. More broadly, our research is expected to provide insights into mechanisms that enable the proper synaptic connectivity in the retina—a requirement for the successful restoration of vision through cell transplantation therapies.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $476,484 )
2025	2025	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Vision Research	000	9	7/28/2025	NON-COMPETING CONTINUATION	$476,484
														Subtotal = $476,484

Issue Date FY: 2024 ( Subtotal = $476,484 )
2024	2024	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Vision Research	000	8	4/30/2024	NON-COMPETING CONTINUATION	$476,484
														Subtotal = $476,484

Issue Date FY: 2023 ( Subtotal = $476,484 )
2023	2023	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Vision Research	002	7	5/25/2023	NON-COMPETING CONTINUATION	$476,484
2023	2022	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Vision Research	001	6	5/22/2023	COMPETING CONTINUATION	$60,600
2023	2021	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Vision Research	000	5	5/22/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$60,600
														Subtotal = $476,484

Issue Date FY: 2022 ( Subtotal = $476,484 )
2022	2022	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Vision Research	001	6	9/20/2022	COMPETING CONTINUATION	$476,484
2022	2021	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Vision Research	000	5	9/20/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $476,484

Issue Date FY: 2021 ( Subtotal = $320,550 )
2021	2021	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR MN 13	AUSTIN	TX	78712	TRAVIS	USA	Vision Research	002	5	4/23/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$320,550
2021	2021	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR MN 13	AUSTIN	TX	78712	TRAVIS	USA	Vision Research	005	5	8/22/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$510,722
2021	2020	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Vision Research	001	4	4/22/2021	SUPPLEMENT FOR EXPANSION	$0
2021	2020	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Vision Research	004	4	8/22/2021	SUPPLEMENT FOR EXPANSION	-$379,137
2021	2020	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Vision Research	000	4	4/22/2021	NON-COMPETING CONTINUATION	$0
2021	2020	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Vision Research	003	4	8/22/2021	NON-COMPETING CONTINUATION	-$131,585
														Subtotal = $320,550

Issue Date FY: 2020 ( Subtotal = $697,092 )
2020	2020	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Vision Research	000	4	2/26/2020	NON-COMPETING CONTINUATION	$317,955
2020	2020	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Vision Research	001	4	8/24/2020	SUPPLEMENT FOR EXPANSION	$379,137
														Subtotal = $697,092

Issue Date FY: 2019 ( Subtotal = $440,291 )
2019	2019	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Vision Research	000	3	2/7/2019	NON-COMPETING CONTINUATION	$440,291
														Subtotal = $440,291

Issue Date FY: 2018 ( Subtotal = $442,356 )
2018	2018	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Vision Research	000	2	3/2/2018	NON-COMPETING CONTINUATION	$398,119
2018	2018	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Vision Research	001	2	6/18/2018	NON-COMPETING CONTINUATION	$44,237
														Subtotal = $442,356

Issue Date FY: 2017 ( Subtotal = $568,557 )
2017	2017	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Vision Research	000	1	2/13/2017	NEW	$568,557
														Subtotal = $568,557

Grand Total All Awards = $4,374,782

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Calcium channels in retinal photoreceptors

Award Number: R01EY026817

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 03/01/2017

PERIOD OF PERFORMANCE END DATE: 04/30/2026

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