U01EY034680

Mechanisms of Pain and Photophobia in Migraine and Dry Eye - Project Summary

Ocular pain and photophobia are common and debilitating conditions associated with migraine and dry eye disease (DED). Persistent pain, dry eye, and/or photophobia are also experienced by nearly 40% of patients who have received refractive surgery.

A common neuroanatomical substrate in migraine, DED, and refractive surgery is the trigeminal nerve, specifically the ophthalmic branch, which is involved in reflex homeostatic regulation of the cornea and dura. It is well known that damage to these reflex circuits leads to overt sensations of pain, yet the underlying mechanisms are poorly understood and effective non-opioid treatments are lacking.

We hypothesize that the trigeminal neurons projecting to the cornea and dura are modulated by feedback from light-sensing cells in the eye, as well as by interaction with infiltrating immune cells leading to dysregulation of the reflex pathways and amplification of sensory responses – causing hypersensitivities to touch and light (photophobia).

We will test this hypothesis in rodent models of migraine, DED, and refractive surgery by identifying molecular mechanisms and neural pathways common to the three pain models, using neuroanatomical, physiological, and behavioral approaches. Experiments will include investigation of potential therapeutic targets, including CGRP, TRPM3, and melanopsin, all of which have been previously implicated in photophobia.

These studies will elucidate key cellular and molecular changes underlying the development of ocular pain and photophobia in migraine, DED, and refractive surgery, and will guide therapeutic development.

Oregon Health & Science University

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]

Portland, Oregon 972393011 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 239% from $1,021,170 to $3,466,540.