Melanopsin-Specific Contributions to Photophobia in Brain Trauma
Abstract
A debilitating, long-term symptom that often accompanies concussion (a.k.a. mild traumatic brain injury or mTBI) is photophobia: discomfort and pain from bright and flickering lights. It is not understood how the neural damage caused by concussion leads to photophobia. What types of nerve injury produce photophobia? Why does the injury have the particular effect of producing photophobia? Is the sensitivity to bright lights and to flickering lights caused by a common biological mechanism or is a different injury associated with each? This lack of understanding means that we do not have objective tests for diagnosing the nature of photophobia in any given person, nor do we know how to target with potential therapies. The eye contains several types of light-sensitive cells. Most of these cells are used to see details and colors. Our approach to understanding photophobia begins with the theory that there are other, special cells in the eye involved in the sense of pain from bright light. These cells contain the protein "melanopsin" and earlier studies in animals suggest that the melanopsin cells are used to sense and adjust to the overall level of light. The goal of the proposed research is to test the specific hypothesis that photophobia in mTBI results from alteration in the function these melanopsin cells. To carry out the research, we have developed a non-invasive technique that allows us to stimulate just the melanopsin containing cells, so that we can examine the function of this system without the responses from other types of light-sensitive cells in the eye. There is little if any risk to subjects who participate in the studies. They will look at flickering lights and we will ask them to report how bright the lights look while we monitor the degree to which they squint as well as how different regions of their brains are activated by the lights. We will take care that the lights are kept at levels that do not cause excessive pain in the patients who suffer from photophobia. As a result of the studies, we will learn how strongly the melanopsin system responds in healthy control subjects and whether it responds differently in patients who have photophobia. In addition, we will learn whether stimulation of the melanopsin system alone causes the characteristic pain associated with photophobia to bright light and whether changes in the interaction between stimulation of melanopsin and signals carried by other types of light-sensitive cells causes discomfort from flickering light. There are two types of clinical application for our research. First, if we confirm that there is a difference in how strongly the melanopsin system responds that is characteristic of photophobia in at least some patients, our techniques may be extended to provide an objective, non-invasive diagnostic test for this type of photophobia. This positive patient-related outcome might be expected within a few years after completion of our research, as the technology makes its way from the lab into the clinic. Having an objective biomarker for diagnosis in turn should provide guidance about potential therapies. For example, it may be possible to use the knowledge we gain to individually tailor specific types of sunglasses to minimize the debilitating effects of photophobia. Indeed, one specific hypothesis we will test as part of our research concerns the possibility that photophobia can be reduced by maximizing the amount of light that reaches the eye at some wavelengths while minimize the amount of light that reaches the eye at other wavelengths, with the exact design varying by patient, lighting condition, and what we discover about how the melanopsin system interacts with signals from other types of light-sensitive cells. In the longer run, there is the potential for the development of drugs that either activate or inhibit the melanopsin system, and our work should clarify what drug development is needed. These therapeutic out
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510447
Entities
People
- Geoffrey Aguirre
Organizations
- United States Army
- University of Pennsylvania