U01EY034692

Effects of Cornea Epithelial Barrier Disruption on the Cornea Trigeminal Neural Circuit - Abstract

This proposal investigates the cornea-trigeminal neural circuit with particular emphasis on the relationship between the cornea epithelium and the intraepithelial nerves. To investigate the hypothesis that ocular surface pathologies that involve transient and/or prolonged corneal epithelial barrier disruption will cause greater nociceptor stimulation, discomfort, pain, and a compensatory reduction in epithelial and stromal nerve density.

Single-cell RNA and epigenetic profiling and in situ hybridization will be performed in corneal and trigeminal ganglion cells that project to the cornea in homeostatic conditions and after epithelial barrier disruption due to dry eye and corneal epithelial debridement. Data from these assays will be integrated, and single-cell atlases of the cornea and trigeminal ganglion under normal and stressed conditions will be generated that identify cells based on unique expression profiles.

Cells will be spatially resolved in these tissues to identify communications between corneal cells and nerve axons and between trigeminal neuronal and non-neuronal cells. In the ganglion, temporally and spatially resolved transcriptomic data will be associated with the changes in corneal epithelial nerve morphology and sensitivity that occur after barrier disruption to identify genes that maintain the corneal epithelial nerves in health and promote the pathological changes after barrier disruption.

Three specific aims are proposed to investigate the cornea-trigeminal circuit. Aim 1 will investigate the effects of barrier disruption from dry eye and epithelial debridement on transcriptomic profiles, corneal epithelial nerve morphology, and nerve function. Aim 2 will investigate the effects of preserving epithelial barrier in the MMP-9 knockout strain in dry eye and epithelial wounding on these parameters, and Aim 3 will investigate the effects of two neural sensitizing chemokines on the circuit in normal and dry eyes.

The proposed experiments investigate the cornea epithelial-trigeminal sensory circuit at a coordinated deep level to identify factors that impact the intraepithelial nerves in health and disease. At the conclusion of this project, we will have a better understanding of the mechanisms by which corneal epithelial cells and intact barrier suppress nerve activation and the factors produced by cornea cells in barrier-disrupted corneas that cause nerve degeneration and heightened sensitivity.

The benchmark accomplishments of this project will be a fundamental new understanding of the impact of corneal epithelial barrier disruption that occurs in common corneal diseases on the integrity and function of the corneal epithelial nerve network.

Baylor College Of Medicine

1) TO SUPPORT EYE AND VISION RESEARCH PROJECTS THAT ADDRESS THE LEADING CAUSES OF BLINDNESS AND IMPAIRED VISION IN THE U.S. THESE INCLUDE RETINAL DISEASES, CORNEAL DISEASES, CATARACT, GLAUCOMA AND OPTIC NEUROPATHIES, STRABISMUS, AMBLYOPIA, AND LOW VISION AND BLINDNESS REHABILITATION. 2) TO INCREASE UNDERSTANDING OF THE NORMAL DEVELOPMENT AND FUNCTION OF THE VISUAL SYSTEM IN ORDER TO BETTER PREVENT, DIAGNOSE, AND TREAT SIGHT-THREATENING CONDITIONS, AND, TO ENHANCE THE REHABILITATION, TRAINING, AND QUALITY OF LIFE OF INDIVIDUALS WHO ARE PARTIALLY-SIGHTED OR BLIND. 3) TO SUPPORT A BROAD PROGRAM OF BASIC VISION RESEARCH THROUGH GRANTS AND COOPERATIVE AGREEMENTS, TO ENCOURAGE HIGH QUALITY CLINICAL RESEARCH, INCLUDING CLINICAL TRIALS, OTHER EPIDEMIOLOGICAL STUDIES, AND HEALTH SERVICES RESEARCH, TO ENCOURAGE RESEARCH TRAINING AND CAREER DEVELOPMENT IN THE SCIENCES RELATED TO VISION, AND TO SPONSOR SCIENTIFIC WORKSHOPS IN HIGH PRIORITY RESEARCH AREAS TO ENCOURAGE EXCHANGE OF INFORMATION AMONG SCIENTISTS. 4) SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO ENCOURAGE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.867 - Vision Research

National Eye Institute (NEI) [HHS - NIH]

Houston, Texas 770303411 United States

Single Zip Code

Ocular Surface Innervation from Cell Types to Circuit Functions (U01 Clinical Trial Not Allowed) (RFA-EY-21-004)

Amendment Since initial award the total obligations have increased 297% from $1,193,265 to $4,737,185.