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Mechanisms of Neuroregulation of Corneal Angiogenesis

Award Number: R01EY038179
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/30/2026
PERIOD OF PERFORMANCE END DATE: 06/30/2031

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Mechanisms of Neuroregulation of Corneal Angiogenesis - The angiogenic privilege of the cornea refers to its normal avascularity, and loss of such privilege leads to pathological angiogenesis and subsequent corneal opacity, decreased vision, and higher risks of transplant failure. The cornea is abundantly innervated by sensory nerves derived from the trigeminal ganglion. Degeneration of these nerves leads to neurotropic corneas at risk for persistent epithelial defect, ulceration and even perforation. Our preliminary data revealed that sensory neurons suppress vascular endothelial cell activation and that neurotrophic corneas have heightened angiogenic and inflammatory responses. This proposal aims to determine how sensory nerves maintain corneal angiogenic privilege and how their degeneration promotes pathological angiogenesis. We will utilize an ex vivo co-culture system of vascular endothelial cells and sensory neurons and an in vivo transgenic mouse model with corneal nerve degeneration to study the following three specific aims. Aim 1 investigates the angiogenic response in normal versus neurotrophic corneas by comparing the effects of normal and degenerative sensory nerves on vascular endothelial cell activities in vitro and corneal angiogenesis in vivo. Aim 2 focuses on the role of neuropeptide alpha-melanocyte-stimulating hormone and its melanocortin receptor 1 in suppressing angiogenesis and examines the therapeutic effect of activating their signaling in treating angiogenesis in neurotrophic corneas. Aim 3 examines immune cell contributions to the neuroregulation of corneal angiogenesis by profiling immune cell population in neurotrophic corneas, assessing their interaction with sensory neurons, and determining their roles in mediating inflammatory angiogenesis in neurotrophic corneas by selective depletion of myeloid immune cells. In summary, this proposal investigates the direct inhibition of corneal angiogenesis by sensory nerves with emphasis on the roles of vascular endothelial and immune cells, and further explores how dysfunction of these mechanisms in neurotrophic corneas leads to heightened vascular response. This is of high relevance in ocular and non-ocular diseases characterized by peripheral nerve degeneration. Successful completion of this project will not only fill in the knowledge gap in the neuroregulation of corneal angiogenesis but may lead to the development of potential therapeutics for mitigating pathological angiogenesis and regenerating sensory nerves.


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 = $654,589 )
2026	2026	TUFTS MEDICAL CENTER PARENT, INC.	800 WASHINGTON ST	BOSTON	MA	02111	SUFFOLK	USA	Vision Research	000	1	9/17/2026	NEW	$654,589
														Subtotal = $654,589

Grand Total All Awards = $654,589

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Mechanisms of Neuroregulation of Corneal Angiogenesis

Award Number: R01EY038179

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/30/2026

PERIOD OF PERFORMANCE END DATE: 06/30/2031

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