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Longitudinal Intravital Multiphoton Imaging of the Murine Intervertebral Disc to Reveal Age-Associated Mechanisms of Degeneration

Award Number: R21AG103392
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/15/2026
PERIOD OF PERFORMANCE END DATE: 07/31/2029

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Longitudinal Intravital Multiphoton Imaging of the Murine Intervertebral Disc to Reveal Age-Associated Mechanisms of Degeneration - This project aims to establish and characterize an optical implant for intravital multiphoton microscopy of the murine intervertebral disc (IVD), enabling longitudinal visualization of cellular and matrix dynamics. The IVD is a critical fibrocartilage tissue situated between the bony vertebrae of the spine. Injury or age-related IVD degeneration is a driver of chronic low back pain, a condition affecting over 600 million people across the globe. Despite decades of research, there are no treatments available that restore IVD structure and function or prevent continued degeneration, highlighting a pressing clinical need for improved regenerative therapies. A major barrier to IVD research is the lack of ability to spatially resolve cell and matrix dynamics over the time course of degenerative changes and tissue repair, limiting our mechanistic understanding of IVD pathology. Current intravital imaging approaches are limited in resolution (≥ 10 µm) and are therefore unable to provide cellular- level assessments of IVD health. To address this, we propose an innovative approach using a right-angle prism placed adjacent to the spine, redirecting the laser 90° to focus on the IVD. Our preliminary data demonstrates the feasibility of using a prism to visualize collagen fibers and cells in the IVD. Further, we have incorporated the prism in an optical implant that has been well-tolerated in mice for up to 30 days. This intravital imaging method is the first to obtain sub-micrometer scale resolution in live mice, providing opportunities for new data and perspectives to mechanistically study IVD health and degeneration. Our approach allows for the characterization of matrix and cell dynamics within an individual animal rather than euthanizing mice at each time point, reducing the number of animals required and increasing experimental insight through repeated measures. Mice demonstrate similar IVD pathology compared to humans in terms of structure, mechanical properties, and low back pain phenotypes, providing a relevant intact organism model for IVD pathology. Our aims are designed to establish this method for longitudinal intravital imaging of the IVD. Aim 1 focuses on rigorously characterizing the imaging capabilities and reproducibility of the optical implant. We hypothesize that the optical implant will provide a window for intravital imaging of the murine IVD (i) for up to 12-weeks, (ii) with ≤ 5 µm axial and lateral resolution. Imaging performance will be assessed using transgenic mouse models with fluorescent IVD-resident cells. Aim 2 will evaluate the spatiotemporal dynamics of vascular invasion, circulating leukocyte infiltration, and collagen remodeling in a spontaneous, age-progressive model of IVD degeneration. We hypothesize that collagen remodeling will preferentially develop in areas of elevated vascular invasion and leukocyte infiltration. By capturing IVD cell–matrix interactions over time, this project will uncover how degeneration unfolds and identify key windows for intervention. This work will establish a powerful new methodology for spine research, laying the foundation for future NIH proposals in spine health, aging, and 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 = $599,180 )
2026	2026	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Aging Research	000	1	8/10/2026	NEW	$599,180
														Subtotal = $599,180

Grand Total All Awards = $599,180

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Longitudinal Intravital Multiphoton Imaging of the Murine Intervertebral Disc to Reveal Age-Associated Mechanisms of Degeneration

Award Number: R21AG103392

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/15/2026

PERIOD OF PERFORMANCE END DATE: 07/31/2029

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