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Identification of genes involved in photoreceptor recognition and synapse formation

Award Number: R00EY030144
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2023
PERIOD OF PERFORMANCE END DATE: 02/28/2026

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Identification of genes involved in photoreceptor recognition and synapse formation - PROJECT SUMMARY/ABSTRACT Vision loss caused by the death of photoreceptors is a leading cause of irreversible blindness worldwide, yet therapeutic options remain limited. For this reason, the NEI's Retinal Disease Program has identiﬁed the development of strategies for the treatment of retinal degenerations as a core program goal. Recently, several laboratories have derived photoreceptors from stem cells, making cell-replacement therapies particularly promising. Additionally, important advances have been made into manipulations that could stimulate retinal regeneration from the retinal Müller glia. The critical barrier for the success of such therapies is the integration of derived photoreceptors into existing retinal circuits to reestablish their function. Yet, we still lack a complete understanding on the mechanisms that underlie the normal wiring of photoreceptors into retinal circuits, especially for cone photoreceptors. Cone photoreceptors of different subtypes are wired into speciﬁc retinal circuits, so that functional differences (like spectral sensitivity) may be exploited to extract speciﬁc information (like color) from the visual scene. Our main hypothesis for this proposal is that each cone subtype expresses speciﬁc genes that allow recognition by its postsynaptic partners (bipolar and horizontal cells), and our main goal is to identify these genes. To accomplish this, we will ﬁrst generate a complete transcriptomic proﬁling of the four different cone subtypes in zebraﬁsh, and identify genes that are differentially expressed (aim #1). Based on this differential expression, we will perform a reverse-genetic screen, where we will assess the functional, structural and ultrastructural integrity of the cone synapses (aim #2). This will allow us to identify genes that control the control the formation of synapses between cones and other retinal cells, and that promote the integration of cones into retinal circuits. We believe that this new knowledge could have direct applications in the improvement of cell-replacement or regenerative therapies for retinal degenerations. Moreover, wiring speciﬁcity is a key feature of neural circuits in general. This proposal beneﬁts from the experimental accessibility of the retina and our deep knowledge of retinal cell types and circuits, but our approach has the potential to impact the study of other neuronal degenerative diseases.


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 = $243,239 )
2025	2025	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BUILDING	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Vision Research	000	4	3/27/2025	NON-COMPETING CONTINUATION	$243,239
														Subtotal = $243,239

Issue Date FY: 2024 ( Subtotal = $246,176 )
2024	2024	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BUILDING	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Vision Research	000	3	3/1/2024	NON-COMPETING CONTINUATION	$246,176
														Subtotal = $246,176

Issue Date FY: 2023 ( Subtotal = $249,000 )
2023	2023	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Vision Research	000	2	5/9/2023	EXTENSION WITH OR WITHOUT FUNDS	$249,000
														Subtotal = $249,000

Grand Total All Awards = $738,415

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Identification of genes involved in photoreceptor recognition and synapse formation

Award Number: R00EY030144

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/01/2023

PERIOD OF PERFORMANCE END DATE: 02/28/2026

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