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Morphologic and Functional Assessment of Field-Potentiated Optic Nerve Regeneration

Award Number: R01EY035715
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2024
PERIOD OF PERFORMANCE END DATE: 07/31/2025

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Morphologic and Functional Assessment of Field-Potentiated Optic Nerve Regeneration - Project Summary To date, no therapy exists to restore vision to the over 64 million people worldwide who are legally blind from diseases that damage the optic nerve. Neuro-protective strategies aimed at preventing damaged retinal ganglion cells (RGCs) from degenerating and neuro-regenerative strategies aimed at promoting axon growth confer modest gains in vision after optic nerve crush injury when applied alone. Moreover, these approaches appear to be lacking in guidance cues as regenerating RGC axons have been reported to have circuitous projections, with 10-20% of axons exhibiting premature branching and 40% of axons having regenerated aberrantly, making u-turns and extending back towards the eye or growing into the opposite optic nerve. We have shown that exogenously applied electric fields (EFs) not only promote RGC axon growth but appear to also be able to control the direction of axon growth. This suggests that EFs may be exploited to not only “drive” axon growth but also “steer” axons to grow towards intended targets. Indeed, in vivo stimulation with asymmetric waveforms was found to be effective at directing full-length optic nerve regeneration, without evidence of aberrant targeting, and restoring partial visual function (local field potential recordings in the superior colliculus and pattern electroretinogram) after crush injury. Given this, we hypothesized that combining EF stimulation with other neuro-regenerative strategies would have synergistic effects on promoting optic nerve regeneration. More targeted regeneration could confer increased gains in visual function. Our multi-disciplinary consortium between neuro-ophthalmologists, developmental biologists, neuro-anatomists, neurosurgeons, electrophysiologists, and electrical engineers proposes to test the efficacy of combining neuro-protective and neuro- regenerative strategies with EF application to direct RGC axon regeneration and restore visual function to adult rats after optic nerve crush injury. Additionally, we will map and characterize the morphology and trajectory of regenerated axons in whole rat brains using 3D light sheet microscopy and SHIELD tissue clearing histology and assess whether EFs direct target specific regeneration.


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: 2026 ( Subtotal = $0 )
2026	2025	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Vision Research	000	2	12/12/2025	NON-COMPETING CONTINUATION	-$467,447
2026	2025	UNIVERSITY OF CALIFORNIA IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Vision Research	001	3	12/19/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$467,447
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $646,761 )
2025	2025	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Vision Research	000	2	3/17/2025	NON-COMPETING CONTINUATION	$646,761
														Subtotal = $646,761

Issue Date FY: 2024 ( Subtotal = $578,213 )
2024	2024	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90089	LOS ANGELES	USA	Vision Research	000	1	2/29/2024	NEW	$578,213
														Subtotal = $578,213

Grand Total All Awards = $1,224,974

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Morphologic and Functional Assessment of Field-Potentiated Optic Nerve Regeneration

Award Number: R01EY035715

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/01/2024

PERIOD OF PERFORMANCE END DATE: 07/31/2025

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