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Chimeric model for study of human retinal microglia in vivo

Award Number: R21EY037023
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2025
PERIOD OF PERFORMANCE END DATE: 01/31/2027

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Chimeric model for study of human retinal microglia in vivo - PROJECT SUMMARY Microglia, the resident innate immune cells of the CNS, play essential roles in CNS development and homeostasis, and are key responders to neuronal stress, injury and disease, including in retina. While retinal microglia have been well characterized in rodent models, much less is known about the properties and responses of human retinal microglia, particularly in an in vivo context. To address this, we seek to establish a model to study human microglia in vivo in the context of the retina. Here we will introduce human induced pluripotent stem cell derived hematopoietic progenitor cells (iHPCs) into the newborn murine brain and assess engraftment of the resulting human xenotransplanted microglia (xMGs) in the retina. In the first aim, we will characterize the engraftment, including density and distribution, of xMGs into mouse retina and optic nerve, and will determine the impact on host retinal cells and tissue organization. In the second aim we will use single cell RNA sequencing to define the human xMG transcriptome, will compare gene expression to endogenous human microglia, and finally will analyze xMG responses via transcriptional changes to optic nerve crush, a well characterized axon injury model resulting in retinal ganglion cell degeneration. This study will provide critical foundational insight into the properties of human xMGs integrated into the mouse retina and test their responses to retinal ganglion cell injury, providing a potentially powerful resource for studying in vivo human retinal microglia responses to injury, disease or 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 = $195,300 )
2026	2026	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Vision Research	000	2	1/29/2026	NON-COMPETING CONTINUATION	$195,300
														Subtotal = $195,300

Issue Date FY: 2025 ( Subtotal = $247,700 )
2025	2025	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Vision Research	000	1	1/22/2025	NEW	$247,700
														Subtotal = $247,700

Grand Total All Awards = $443,000

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Chimeric model for study of human retinal microglia in vivo

Award Number: R21EY037023

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/01/2025

PERIOD OF PERFORMANCE END DATE: 01/31/2027

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