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Phototransduction in health and disease

Award Number: R01EY012155
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Phototransduction in health and disease - Abstract Cyclic GMP and calcium (Ca2+) are effectors of phototransduction and maintenance of their homeostasis is critical for photoreceptor cell health and function. Indeed, perturbance of this homeostasis is thought to be a primary driver of cell death in different forms of retinal degenerations. For example, mutations affecting phototransduction genes leading to elevated cGMP is expected to cause toxic Ca2+ influx into the outer segment via the cGMP-gated channels. Although a reasonable hypothesis, it is difficult to reconcile with 1) the cell death machinery is localized in the inner segment, and 2) the current dogma that the outer and inner segments Ca2+ are compartmentalized and insulated from each other. This raises an important and unanswered question: how does [Ca2+] buildup in the outer segment alter [Ca2+] in the inner segment to activate cell death? Our central hypothesis is that altered Ca2+ homeostasis at the outer segment leads to mitochondrial stress at the inner segment. This, in turn, allows Ca2+ to equilibrate with the proximal cell compartments where the cell death machinery resides. To test this hypothesis, we will use mouse models that express genetically encoded, ratiometric Ca2+ indicators in retinal rods and cones. To prevent activating the photoreceptor cells, we will use 1) a multiphoton microscope equipped with a super-sensitive HyD detector that images under extremely low photon flux and 2) mouse models with attenuated phototransduction to reduce Ca2+ feedback. Using retinae obtained from both male and female mice, we will image [Ca2+]i from different cellular compartments simultaneously, in both dark adapted and light exposed conditions, in healthy and degenerating photoreceptors, to visualize how changes in [Ca2+] in one cellular compartment may affect [Ca2+] in another compartment. The proposed experiments should provide a better understanding of the role of Ca2+ homeostasis in health and disease.


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 = $559,584 )
2025	2025	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Vision Research	001	23	3/14/2025	NON-COMPETING CONTINUATION	$559,584
2025	2022	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Vision Research	000	21	2/11/2025	COMPETING CONTINUATION	$0
														Subtotal = $559,584

Issue Date FY: 2024 ( Subtotal = $559,444 )
2024	2024	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90089	LOS ANGELES	USA	Vision Research	001	22	5/22/2024	COMPETING CONTINUATION	$559,444
2024	2022	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90089	LOS ANGELES	USA	Vision Research	000	21	5/21/2024	COMPETING CONTINUATION	$0
														Subtotal = $559,444

Issue Date FY: 2022 ( Subtotal = $412,500 )
2022	2022	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Vision Research	000	21	9/20/2022	COMPETING CONTINUATION	$412,500
														Subtotal = $412,500

Issue Date FY: 2021 ( Subtotal = -$5,421 )
2021	2018	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Vision Research	000	20	6/29/2021	NON-COMPETING CONTINUATION	-$5,421
														Subtotal = -$5,421

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2018	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Vision Research	000	20	5/11/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $625,836 )
2018	2018	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER STREET THIRD FLOOR	LOS ANGELES	CA	90089	LOS ANGELES	USA	Vision Research	000	20	1/11/2018	NON-COMPETING CONTINUATION	$563,252
2018	2018	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER STREET THIRD FLOOR	LOS ANGELES	CA	90089	LOS ANGELES	USA	Vision Research	001	20	5/22/2018	NON-COMPETING CONTINUATION	$62,584
														Subtotal = $625,836

Issue Date FY: 2017 ( Subtotal = $625,836 )
2017	2017	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER STREET THIRD FLOOR	LOS ANGELES	CA	90089	LOS ANGELES	USA	Vision Research	000	19	1/26/2017	NON-COMPETING CONTINUATION	$563,252
2017	2017	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER STREET THIRD FLOOR	LOS ANGELES	CA	90089	LOS ANGELES	USA	Vision Research	001	19	7/24/2017	NON-COMPETING CONTINUATION	$62,584
														Subtotal = $625,836

Issue Date FY: 2016 ( Subtotal = $642,086 )
2016	2016	UNIVERSITY OF SOUTHERN CALIFORNIA	3500 SOUTH FIGUEROA STREET 102	LOS ANGELES	CA	90089	LOS ANGELES	USA	Vision Research	001	18	2/9/2016	COMPETING CONTINUATION	$642,086
2016	2014	UNIVERSITY OF SOUTHERN CALIFORNIA	3500 SOUTH FIGUEROA STREET 102	LOS ANGELES	CA	900898001	LOS ANGELES	USA	Vision Research	000	17	2/4/2016	NON-COMPETING CONTINUATION	$0
														Subtotal = $642,086

Issue Date FY: 2014 ( Subtotal = $619,122 )
2014	2014	UNIVERSITY OF SOUTHERN CALIFORNIA	3500 SOUTH FIGUEROA STREET 102	LOS ANGELES	CA	90089	LOS ANGELES	USA	Vision Research	000	17	4/28/2014	NON-COMPETING CONTINUATION	$619,122
														Subtotal = $619,122

Issue Date FY: 2013 ( Subtotal = $575,742 )
2013	2013	UNIVERSITY OF SOUTHERN CALIFORNIA	3500 SOUTH FIGUEROA STREET 102	LOS ANGELES	CA	90089	LOS ANGELES	USA	Vision Research	000	16	5/2/2013	NON-COMPETING CONTINUATION	$545,439
2013	2013	UNIVERSITY OF SOUTHERN CALIFORNIA	3500 SOUTH FIGUEROA STREET 102	LOS ANGELES	CA	90089	LOS ANGELES	USA	Vision Research	001	16	6/12/2013	NON-COMPETING CONTINUATION	$30,303
														Subtotal = $575,742

Issue Date FY: 2012 ( Subtotal = $602,705 )
2012	2012	UNIVERSITY OF SOUTHERN CALIFORNIA	3500 SOUTH FIGUEROA STREET 102	LOS ANGELES	CA	90089	LOS ANGELES	USA	Vision Research	000	15	4/30/2012	COMPETING CONTINUATION	$602,705
2012	2011	UNIVERSITY OF SOUTHERN CALIFORNIA	3500 SOUTH FIGUEROA STREET 102	LOS ANGELES	CA	90089	LOS ANGELES	USA	Vision Research	001	14	4/30/2012	NON-COMPETING CONTINUATION	$0
														Subtotal = $602,705

Issue Date FY: 2011 ( Subtotal = $556,942 )
2011	2011	UNIVERSITY OF SOUTHERN CALIFORNIA	3500 SOUTH FIGUEROA STREET 102	LOS ANGELES	CA	90089	LOS ANGELES	USA	Vision Research	000	14	2/18/2011	NON-COMPETING CONTINUATION	$522,134
2011	2011	UNIVERSITY OF SOUTHERN CALIFORNIA	3500 SOUTH FIGUEROA STREET 102	LOS ANGELES	CA	90089	LOS ANGELES	USA	Vision Research	001	14	5/26/2011	NON-COMPETING CONTINUATION	$34,808
														Subtotal = $556,942

Issue Date FY: 2010 ( Subtotal = $588,040 )
2010	2010	UNIVERSITY OF SOUTHERN CALIFORNIA	3500 SOUTH FIGUEROA STREET 102	LOS ANGELES	CA	90089	LOS ANGELES	USA	Vision Research	000	13	2/24/2010	NON-COMPETING CONTINUATION	$588,040
														Subtotal = $588,040

Issue Date FY: 2009 ( Subtotal = $590,162 )
2009	2009	UNIVERSITY OF SOUTHERN CALIFORNIA	3500 SOUTH FIGUEROA STREET 102	LOS ANGELES	CA	90089	LOS ANGELES	USA	Vision Research	000	12	2/9/2009	NON-COMPETING CONTINUATION	$531,146
2009	2009	UNIVERSITY OF SOUTHERN CALIFORNIA	3500 SOUTH FIGUEROA STREET 102	LOS ANGELES	CA	90089	LOS ANGELES	USA	Vision Research	001	12	4/20/2009	NON-COMPETING CONTINUATION	$59,016
														Subtotal = $590,162

Issue Date FY: 2008 ( Subtotal = $649,278 )
2008	2008	UNIVERSITY OF SOUTHERN CALIFORNIA	3500 SOUTH FIGUEROA STREET 102	LOS ANGELES	CA	90089	LOS ANGELES	USA	Vision Research	000	11	2/18/2008	COMPETING CONTINUATION	$649,278
														Subtotal = $649,278

Issue Date FY: 2007 ( Subtotal = $464,102 )
2007	2007	UNIVERSITY OF SOUTHERN CALIFORNIA	3500 SOUTH FIGUEROA STREET 102	LOS ANGELES	CA	90089	LOS ANGELES	USA	Vision Research	000	10	3/16/2007	NON-COMPETING CONTINUATION	$464,102
														Subtotal = $464,102

Issue Date FY: 2006 ( Subtotal = $485,274 )
2006	2006	UNIVERSITY OF SOUTHERN CALIFORNIA	3500 SOUTH FIGUEROA STREET 102	LOS ANGELES	CA	90089	LOS ANGELES	USA	Vision Research	000	9	2/2/2006	NON-COMPETING CONTINUATION	$485,274
														Subtotal = $485,274

Issue Date FY: 2005 ( Subtotal = $484,931 )
2005	2005	UNIVERSITY OF SOUTHERN CALIFORNIA	3500 SOUTH FIGUEROA STREET 102	LOS ANGELES	CA	90089	LOS ANGELES	USA	Vision Research	000	8	2/28/2005	NON-COMPETING CONTINUATION	$484,931
														Subtotal = $484,931

Issue Date FY: 2004 ( Subtotal = $463,484 )
2004	2004	UNIVERSITY OF SOUTHERN CALIFORNIA	1014 CHILDS WAY	LOS ANGELES	CA	90089	LOS ANGELES	USA	Vision Research	000	7	2/23/2004	NON-COMPETING CONTINUATION	$463,484
														Subtotal = $463,484

Issue Date FY: 2003 ( Subtotal = $449,922 )
2003	2003	UNIVERSITY OF SOUTHERN CALIFORNIA	1014 CHILDS WAY	LOS ANGELES	CA	90089	LOS ANGELES	USA	Vision Research	000	6		COMPETING CONTINUATION	$449,922
														Subtotal = $449,922

Issue Date FY: 2002 ( Subtotal = $419,999 ) (Continued on the next page)
Grand Total All Awards = $11,918,182

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Phototransduction in health and disease

Award Number: R01EY012155

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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