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Retinal sheet transplant impact on functional organization of visual cortex in retinal degenerate animal models

Award Number: R01EY032948
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2022
PERIOD OF PERFORMANCE END DATE: 03/31/2026

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Retinal sheet transplant impact on functional organization of visual cortex in retinal degenerate animal models - Millions of people worldwide suffer vision loss from progressed stages of age-related macular degeneration and retinitis pigmentosa. Through the disease, much of the retinal pigment epithelium (RPE) and many photoreceptors are irreversibly lost and new cutting edge treatments using trophic factors or gene therapy are ineffective because the tissues are no longer present to be rescued. Our goal is to remediate vision loss through transplantation of retinal progenitor tissue sheets into the degenerated retina. In rodent models of retinal degeneration (RD), several studies have demonstrated that retinal progenitor sheets successfully integrate into the host retina, through synaptic connectivity between the transplant retina and host, and evoke responses to flashes of light in the superior colliculus (SC, a midbrain visual nucleus and direct target of retinal ganglion cells). However, in order to determine the complexity and quality of visual information provided by the transplant visual responsivity must be determined at a greater level of detail and in structures such as higher visual cortex where more complex visual processing occurs. Our main hypothesis is that transplants of fetal- and hESC-derived retinal progenitor sheets will drive complex and specialized visual responses in visual cortex (Aims 1 and 2), as well as visually guided behavior, and, that feedforward and feedback cortical circuitry at the level of specific neuronal cell types will be more similar to normal rats than RD rats without transplants (Aim 3). These studies will be performed using two rat models that are effectively blind by 3 months of age - through a collaboration combining visual neurophysiology expertise and cutting edge neural circuit tracing using genetically modified rabies viruses from the PI with the unrivaled surgical skills for retinal sheet transplantation and expert breeding knowledge of transgenic RD rats by the CO-PI. This project directly addresses the NEI Audacious Goals Initiative to regenerate the eye and visual system.


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 = $575,017 )
2025	2025	UNIVERSITY OF CALIFORNIA IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Vision Research	000	4	3/14/2025	NON-COMPETING CONTINUATION	$575,017
														Subtotal = $575,017

Issue Date FY: 2024 ( Subtotal = $583,625 )
2024	2024	UNIVERSITY OF CALIFORNIA IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Vision Research	000	3	4/30/2024	NON-COMPETING CONTINUATION	$583,625
														Subtotal = $583,625

Issue Date FY: 2023 ( Subtotal = $587,076 )
2023	2023	UNIVERSITY OF CALIFORNIA, IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Vision Research	000	2	4/3/2023	NON-COMPETING CONTINUATION	$587,076
														Subtotal = $587,076

Issue Date FY: 2022 ( Subtotal = $595,144 )
2022	2022	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Vision Research	000	1	4/22/2022	NEW	$595,144
														Subtotal = $595,144

Grand Total All Awards = $2,340,862

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Retinal sheet transplant impact on functional organization of visual cortex in retinal degenerate animal models

Award Number: R01EY032948

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/2022

PERIOD OF PERFORMANCE END DATE: 03/31/2026

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