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Contact Lens Wear, Bacteria, and Corneal Homeostasis

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: 05/01/2019
PERIOD OF PERFORMANCE END DATE: 01/31/2025

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Contact Lens Wear, Bacteria, and Corneal Homeostasis - Summary: Worn by >40 million people in the USA alone, contact lenses are associated with a risk of sight-threatening infection. With increasing use for myopia prevention and efforts to develop lenses for technological purposes, a surge in lens usage (extended wear specifically) is predicted. Unfortunately, research related to lens-related complications has been hindered by lack of an in vivo model amenable to the many research tools available only for mice. Following a 25-year effort, we have developed a mouse contact lens wear model. This utilizes silicone hydrogel lenses custom made by a contact lens manufacturer to fit mouse eyes, and does not require lid suturing. The lenses enable corneal infection when contaminated with P. aeruginosa, the most common causative agent of contact lens-related keratitis in people. Foundational to understanding contact lens related infection is knowing how a lens impacts the cornea without bacterial inoculation. Preliminary data show the mouse model replicates multiple events occurring during human lens wear, including colonization of the lens with commensal-type bacteria, and a dendritic cell (DC) response within 24 h. Moving beyond what is feasible using human subjects, high resolution time-lapse imaging of mice with fluorescent cell membranes revealed normally not present motile cells resembling neutrophils in the stroma after 6 days of wear. Immunohistochemistry confirmed infiltration of Ly6G+ cells (neutrophil marker). This DC/Ly6G+ response without pathology fits the definition of parainflammation as “a low-grade inflammatory response at an intermediate state between tissue homeostasis and classic inflammation which can be induced by persistent tissue stress…” The three aims of this project will explore; 1) triggers of parainflammation during contact lens wear, 2) how the signal is transduced within the cornea to drive the Ly6G+ cell response, and 3) its significance during microbe challenge. The hypothesis, based on published and preliminary data, is that parainflammation during contact lens wear in mice can be triggered by microbes colonizing the lens, initiating a sequence of events not otherwise occurring in the normally microbiome-free cornea that function to protect it against commensal-type bacteria, but which primes the cornea to respond overly-aggressively to P. aeruginosa. !


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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Contact Lens Wear, Bacteria, and Corneal Homeostasis

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: 05/01/2019

PERIOD OF PERFORMANCE END DATE: 01/31/2025

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