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In Vivo Function and Metabolism Evaluation of Glaucomatous RGCs by Two-Photon Scanning Laser Ophthalmology

Award Number: R01EY034353
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2023
PERIOD OF PERFORMANCE END DATE: 03/31/2028

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In Vivo Function and Metabolism Evaluation of Glaucomatous RGCs by Two-Photon Scanning Laser Ophthalmology - PROJECT SUMMARY Glaucoma, the most common worldwide cause of irreversible blindness, is characterized by progressive dysfunction and death of retinal ganglion cells (RGCs). We recently employed confocal scanning laser ophthalmoscopy (cSLO) to successfully obtain in vivo Ca2+ imaging with mouse RGCs expressing jGCaMP7s, a genetically encoded calcium indicator. Thousands of ON, OFF, and ON-OFF RGCs with characteristic responses to light stimulation are readily detected in living animals through this non-invasive in vivo imaging platform. Here we seek to develop a more advanced, first-of-its-kind two-photon (2P)-SLO platform with patterned stimulation and multiple detection channels. Through a multidisciplinary collaboration with expertise in in vivo optical imaging, RGC pathophysiology, and retinal neural circuitry and visual processing, we will use complementary imaging techniques and state-of-the-art analysis protocols to understand naïve RGC physiology in real time. We recently extended our original mouse silicone oil-induced pupillary blocking and ocular hypertension (SOHU) model to recapitulate phenotypes of two forms of glaucoma: a chronic model with moderate IOP elevation and mild RGC neurodegeneration; and an acute model with greatly elevated IOP and severe neurodegeneration. Importantly, SO removal reduces IOP to normal almost immediately, allowing better exploration of the effects of IOP lowering treatment and combined treatment with neuroprotection strategies. Thus, we will determine the longitudinal functional and metabolic changes of glaucomatous RGCs, under clinically relevant models, both before and after IOP normalization and/or neuroprotective treatments. These data will deepen our understanding of the pathophysiology of glaucoma, towards finding much-sought biomarkers to better predict progression, and create more relevant endpoints for developing treatment to restore RGC physiology in vivo.


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: 2025 ( Subtotal = $746,153 )
2025	2025	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Vision Research	000	3	3/28/2025	NON-COMPETING CONTINUATION	$746,153
														Subtotal = $746,153

Issue Date FY: 2024 ( Subtotal = $671,615 )
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Vision Research	000	2	3/13/2024	NON-COMPETING CONTINUATION	$671,615
														Subtotal = $671,615

Issue Date FY: 2023 ( Subtotal = $641,549 )
2023	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Vision Research	000	1	6/22/2023	NEW	$641,549
														Subtotal = $641,549

Grand Total All Awards = $2,059,317

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In Vivo Function and Metabolism Evaluation of Glaucomatous RGCs by Two-Photon Scanning Laser Ophthalmology

Award Number: R01EY034353

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2023

PERIOD OF PERFORMANCE END DATE: 03/31/2028

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