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Role of the nerve regeneration-associated gene Sox11 in promoting corneal innervation and epithelial cell repair in dry eye

Award Number: R01EY026145
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Dry eye disease results from an inadequate tear film on the corneal surface that can result in ocular pain and in some cases serious vision problems. Symptoms of dry eye disease are a primary reason for patient visits to ophthalmologists and optometrists in the United States, and for many sufferers treatment remains inadequate. Previous studies demonstrate a clear role for corneal primary afferent neurons in maintaining the corneal epithelium under normal conditions, presumably through the release of factors that prevent epithelial cell apoptosis and stimulate proliferation. However, the role of these sensory neurons in supporting corneal healing under pathological conditions such as dry eye remains unknown. We hypothesize that dry eye disease and its associated corneal damage initiates an injury-response program in corneal afferent neurons that involves the upregulation of nerve regeneration-associated genes, such as the transcription factor Sox11, in the trigeminal ganglion. It is proposed that upregulation of Sox11 in dry eye is critical for maintaining corneal afferent innervation and thus maintaining the trophic support required to promote corneal healing. The aims in this proposal explore the impact of Sox11 expression in the trigeminal ganglion and the role it plays in maintaining corneal afferent innervation and promoting corneal healing in dry eye. Aim 1 will examine the expression of Sox11 and its downstream gene targets in corneal afferent cell bodies of the trigeminal ganglion following induction of dry eye by lacrimal gland excision. Aim 2 will determine the role of Sox11 in maintaining corneal innervation and sensitivity in dry eye, utilizing a transgenic mouse line in which Sox11 is deleted only in small diameter sensory fibers (including corneal primary afferent neurons). The contribution of Sox11 in these neurons to corneal nerve morphology and functional sensitivity will be examined following lacrimal gland excision. Using these same mice, Aim 3 will determine how deletion of Sox11 in corneal primary afferent neurons impacts the condition of the corneal epithelium following lacrimal gland excision. Corneal fluorescein staining and epithelial cell proliferation and apoptosis will be examined. Finally, Aim 4 will utilize a viral vector to drive the overexpression Sox11 in small diameter sensory fibers, including the corneal afferent neurons, to determine if increasing expression of Sox11 in these neurons can further promote or improve corneal healing under dry eye conditions. The proposed studies will elucidate novel mechanisms that, if targeted appropriately, could simultaneously maintain corneal innervation and facilitate corneal healing in patients suffering from dry eye disease.


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: 2022 ( Subtotal = $0 )
2022	2019	UNIVERSITY OF NEW ENGLAND	11 HILLS BEACH RD	BIDDEFORD	ME	04005	YORK	USA	Vision Research	000	4	2/16/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $355,980 )
2019	2019	UNIVERSITY OF NEW ENGLAND	11 HILLS BEACH RD	BIDDEFORD	ME	04005	YORK	USA	Vision Research	000	4	8/13/2019	NON-COMPETING CONTINUATION	$355,980
														Subtotal = $355,980

Issue Date FY: 2018 ( Subtotal = $355,980 )
2018	2018	UNIVERSITY OF NEW ENGLAND	11 HILLS BEACH RD	BIDDEFORD	ME	04005	YORK	USA	Vision Research	000	3	8/20/2018	NON-COMPETING CONTINUATION	$355,980
														Subtotal = $355,980

Issue Date FY: 2017 ( Subtotal = $355,980 )
2017	2017	UNIVERSITY OF NEW ENGLAND	11 HILLS BEACH RD	BIDDEFORD	ME	04005	YORK	USA	Vision Research	000	2	8/14/2017	NON-COMPETING CONTINUATION	$355,980
														Subtotal = $355,980

Issue Date FY: 2016 ( Subtotal = $355,980 )
2016	2016	UNIVERSITY OF NEW ENGLAND	11 HILLS BEACH ROAD	BIDDEFORD	ME	04005	YORK	USA	Vision Research	001	1	8/31/2016	NEW	$6,148
2016	2016	UNIVERSITY OF NEW ENGLAND	11 HILLS BEACH ROAD	BIDDEFORD	ME	04005	YORK	USA	Vision Research	000	1	8/17/2016	NEW	$349,832
														Subtotal = $355,980

Grand Total All Awards = $1,423,920

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Role of the nerve regeneration-associated gene Sox11 in promoting corneal innervation and epithelial cell repair in dry eye

Award Number: R01EY026145

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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