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Galectin-3 and corneal nerve regeneration

Award Number: R01EY035702
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/01/2024
PERIOD OF PERFORMANCE END DATE: 12/31/2028

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Galectin-3 and corneal nerve regeneration - Project Summary/Abstract The avascular cornea is innervated by a dense network of sensory processes derived from the ophthalmic and maxillary regions of the trigeminal ganglion. Corneal nerves provide not only mechanical, chemical, and thermal sensitivity to the front of the eye but also release nutrients and trophic factors that supply the cornea. Structural and functional nerve abnormalities are the hallmarks of neurotrophic keratopathy, a degenerative disease associated with impaired corneal healing and ulceration. These abnormatilies can also be observed in other conditions known to cause corneal damage, such as dry eye. Most therapeutic approaches aimed to promote corneal nerve regeneration focus on providing neurotrophic support. Recently, the U.S. Food and Drug Administration has approved the use of recombinant nerve growth factor eye drops for the treatment of neurotrophic keratopathy, but its use has been associated with several adverse effects and limitations. This proposal centers on a major gap in our understanding of the inhibitory mechanisms hampering corneal nerve regeneration, which could prove important to develop new strategies to promote functional reinnervation. Research during the last decade has consistently found increased levels of the carbohydrate-binding protein galectin-3 in the tear fluid and corneal epithelium of patients with ocular surface disease. Importantly, the areas where increased galectin-3 expression has been observed coincide with the location of intraepithelial nerve terminals and the basal nerve plexus. It is become increasingly clear that multimerization of galectin-3 leads to cross-linking of carbohydrate ligands and the formation of lattice-like structures on plasma membranes essential for regulating cell survival or degeneration. We hypothesize that overabundance of galectin-3 promotes degenerative signaling by interacting with specific surface receptors in peripheral sensory neurons and may constitute an important therapeutic target for the full recovery of nerve sensation in corneal disease. The following specific aims will address this objective: (1) to examine the role of galectin-3 in modulating neurotrophic signaling, (2) to determine the impact of galectin-3 on the neural mechanisms underlying corneal disease, and (3) to investigate whether whether therapeutic inhibition of galectin-3 improves corneal nerve regeneration and sensation. It is anticipated that the successful conclusion of this project will reveal a novel mechanism by which galectin-3 regulates neurotrophic signaling in corneal nerves. Results could potentially advance the field of corneal nerve regeneration by targeting the pathological actions of galectin-3 and lead to the development of novel therapies to promote functional innervation.


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	TUFTS MEDICAL CENTER PARENT, INC.	800 WASHINGTON ST	BOSTON	MA	02111	SUFFOLK	USA	Vision Research	000	2	12/8/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $558,514 )
2025	2025	TUFTS MEDICAL CENTER PARENT, INC.	800 WASHINGTON ST	BOSTON	MA	02111	SUFFOLK	USA	Vision Research	000	2	1/15/2025	NON-COMPETING CONTINUATION	$558,514
														Subtotal = $558,514

Issue Date FY: 2024 ( Subtotal = $490,237 )
2024	2024	TUFTS MEDICAL CENTER PARENT, INC.	800 WASHINGTON ST	BOSTON	MA	02111	SUFFOLK	USA	Vision Research	000	1	12/6/2023	NEW	$490,237
														Subtotal = $490,237

Grand Total All Awards = $1,048,751

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Galectin-3 and corneal nerve regeneration

Award Number: R01EY035702

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/01/2024

PERIOD OF PERFORMANCE END DATE: 12/31/2028

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