Monday, June 30, 2025 6/30/2025

Transient Receptor Potential Ion Channels and Corneal Defense Against Bacterial Adhesion

Award Number: R01EY030350
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: 01/31/2030

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Transient Receptor Potential Ion Channels and Corneal Defense Against Bacterial Adhesion - Project summary/Abstract: Pseudomonas aeruginosa and Staphylococcus aureus are the two most frequent causes of sight- threatening bacterial keratitis in the USA. Infections caused by either pathogen can be difficult to treat, complicated by the ever-evolving problem of antibiotic resistance. Even successful treatment does not always prevent scarring and associated vision loss. Importantly, the healthy cornea is infection resistant, able of avoid adhesion by virtually all pathogens, including large inocula of P. aeruginosa or S. aureus. For over three decades, our lab has focused on understanding this intrinsic resistance to infection, and how its compromise by predisposing factors sets up conditions for infection initiation, focusing on both the cornea and the bacteria. The outcomes have contributed substantially to our knowledge about those topics. The cornea is endowed with a high density of sensory nerve endings, including some polymodal by virtue of their Transient Receptor Potential (TRP) cation channels. These are mostly TRPV1 (Vanilloid), with TRPA1 (Ankyrin) present only on a subset of TRPV1 expressing nerves. Recently, we reported that corneal nerves can modulate the healthy cornea’s susceptibility to bacterial adhesion involving TRPV1 and TRPA1. Our new data show that these two receptor types confer selectivity for pathogen type, with only TRPV1 countering S. aureus adhesion, and TRPA1 instead countering P. aeruginosa - only the latter requiring nerve firing. We further report that while inoculation with either pathogen elicits a TRPV1/A1 and nerve dependent immune cell response, the details differ. P. aeruginosa increases numbers of CD45+ and CD11c+ cells, the CD11c+ cell fraction shifting to being less spherical and closer to the corneal surface. Importantly, the CD11c+ cells contribute to countering bacterial adhesion. S. aureus causes a smaller CD45+ cell response, with no increase to CD11c+ cell numbers, and different changes to immune cell morphology and location - including a shift away from the corneal surface. Here, we aim to better understand how TRPV1 and TRPA1 differentially counter S. aureus and P. aeruginosa adhesion to the healthy murine cornea. Thus, we will compare them more thoroughly for contributions of immune cells (aim 1), direct-acting players at the ocular surface (aim 2), and roles of bacterial ligands (aim 3). The approach will include use of multiple state-of-the-art technologies including flow cytometry in aim 1, and high-resolution mass spectrometry and snRNAseq in aim 2. All three aims have potential to yield novel strategies for preventing infection before pathology and the associated risk of vision loss begins. Meanwhile, they will advance our general understanding of the healthy cornea’s response to microbial challenge, the relationship to neuroinflammation, roles of nerves, TRPA1 and TRPV1 in the cornea, and the biology of the ocular surface and tear fluid.


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 = $501,104 )
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Vision Research	003	6	6/11/2025	COMPETING CONTINUATION	$10
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Vision Research	001	6	1/17/2025	COMPETING CONTINUATION	$501,104
2025	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Vision Research	002	5	6/11/2025	NON-COMPETING CONTINUATION	-$10
2025	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Vision Research	000	5	1/10/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $501,104

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Vision Research	000	2	1/24/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $392,500 )
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Vision Research	000	5	5/2/2023	NON-COMPETING CONTINUATION	$392,500
														Subtotal = $392,500

Issue Date FY: 2022 ( Subtotal = $380,724 )
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Vision Research	000	4	4/18/2022	NON-COMPETING CONTINUATION	$380,724
														Subtotal = $380,724

Issue Date FY: 2021 ( Subtotal = $380,723 )
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 220	BERKELEY	CA	94710	ALAMEDA	USA	Vision Research	000	3	4/22/2021	NON-COMPETING CONTINUATION	$380,723
														Subtotal = $380,723

Issue Date FY: 2020 ( Subtotal = $392,500 )
2020	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 220	BERKELEY	CA	94710	ALAMEDA	USA	Vision Research	000	2	4/6/2020	NON-COMPETING CONTINUATION	$392,500
														Subtotal = $392,500

Issue Date FY: 2019 ( Subtotal = $392,500 )
2019	2019	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 220	BERKELEY	CA	94710	ALAMEDA	USA	Vision Research	000	1	4/24/2019	NEW	$392,500
														Subtotal = $392,500

Grand Total All Awards = $2,440,051

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Transient Receptor Potential Ion Channels and Corneal Defense Against Bacterial Adhesion

Award Number: R01EY030350

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: 01/31/2030

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