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Therapeutic intervention to target human glaucoma pathogenesis

Award Number: R01EY034174
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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Therapeutic intervention to target human glaucoma pathogenesis - Project Abstract Glaucoma is a silent, underdiagnosed, costly and debilitating disease. The prevalence of glaucoma is expected to reach 80 million by 2020. Direct economic costs for the approximately 2 million US citizens with glaucoma amount to $2.9 billion. The disease is complex and to date, treatment options for the disease only include reducing elevated intraocular pressure (IOP). However, patients are sometimes resistant to conventional drug therapies, and it is crucial to identify therapies and develop new treatments for glaucoma that can save retinal ganglion cells (RGCs) from neurodegeneration. Our relevant proposed studies will provide a foundation for developing a new glaucoma therapeutic that is a neurotrophic factor, human Neuritin 1 (hNRN1). The utilization of hNRN1 is twofold; firstly, it enables the development of a soluble therapy that can promote neuroregeneration of RGCs, and secondly, we can validate the neuroprotective effect in control and glaucomatous RGCs under normal and elevated translaminar pressure conditions. These studies will substantiate the therapeutic potential of this therapy for future patient-specific translational research. Further, we will utilize our established novel ex vivo human perfusion model. This model allows for independent regulation of both simulated IOP and intracranial pressure in human donor eyes, which can exploit the effects of translaminar pressure on RGCs by mimicking the in vivo glaucomatous paradigm. The combined use of stem cell technology, collagen constructs, and human donor eye perfusion model is an original approach to study glaucoma. Our goal is to validate the therapeutic effects of neuritin1 in patient RGCs. Our central hypothesis is that increased hNRN1 expression exerts a protective effect against human RGC degeneration caused by glaucomatous NT deprivation and elevated translaminar pressure. To examine this hypothesis, we propose the following specific aims: AIM 1: Determine the neuro-regenerative role of human NRN1 in glaucomatous hiPSC-RGCs. AIM 2: Determine the therapeutic role of hNRN1 to rescue degeneration of HTG RGCs from elevated IOP. AIM 3: Assess the therapeutic potential of hNRN1 in preventing NTG RGC neurodegeneration. Our powerful tools and valuable stem cell resources will have enormous potential for breakthrough discovery. Utilizing hNRN1 as a therapeutic to overcome glaucomatous degeneration of RGCs will allow us to exploit the most significant resources that can be translatable to clinical studies. It will offer a foundation for deciphering survival and regeneration of RGCs due to glaucomatous neurodegeneration.


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 = $391,746 )
2026	2026	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Vision Research	000	3	1/8/2026	NON-COMPETING CONTINUATION	$391,746
														Subtotal = $391,746

Issue Date FY: 2025 ( Subtotal = $391,746 )
2025	2025	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Vision Research	000	2	12/9/2024	NON-COMPETING CONTINUATION	$391,746
														Subtotal = $391,746

Issue Date FY: 2024 ( Subtotal = $391,746 )
2024	2024	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Vision Research	000	1	12/15/2023	NEW	$391,746
														Subtotal = $391,746

Grand Total All Awards = $1,175,238

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Therapeutic intervention to target human glaucoma pathogenesis

Award Number: R01EY034174

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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