RT Journal Article
A1 Matynia, Anna
A1 parikh, sachin
A1 Deot, Neal
A1 kim, paul
A1 Nusinowitz, Steven
A1 Gorin, Michael B
T1 Light Aversion is Dependent on Melanopsin Expressing Cells in a Mouse Model of Ocular Surface Damage
JF Investigative Ophthalmology & Visual Science
JO Invest. Ophthalmol. Vis. Sci.
YR 2015
VO 56
IS 7 
SP 5566
OP 5566
SN 1552-5783
AB  Sensitivity to normal light levels can negatively impact productivity and quality of life, and is a clinical problem of increasing concern and interest. Corneal surface damage from dry eye disease, LASIK, corneal abrasions, inflammation or neuropathy is associated with photoallodynia, a painful response to normal light. We used corneal surface damage in mice to assess light aversion as a surrogate for photoallodynia. Light aversion was tested using a customized behavioral test (0=no aversion, 1=complete aversion) in wild type (WT) and mice lacking melanopsin expressing cells (OPN4DTA/DTA) with corneal application of benzalkonium chloride (BAC). Corneas were visualized with fluorescein staining, and corneal sensitivity tested using von Frey fibers (0=no blink, 1=reduced partial blink, 2=complete blink). Light aversion increased with increasing concentration of BAC at 1 day (WT AI: 2% BAC, 0.62+/-0.06, n=14; 0.5% BAC, 0.45+/-0.08, n=10, 0.25% BAC, 0.33+/-0.10, n=9; Buffer, 0.19+/-0.08, n=10). OPN4DTA/DTA mice did not exhibit BAC-induced light aversion (AI: 2% BAC, 0.10+/-0.11, n=15; 0.5% BAC, 0.15+/-0.09, n=9, 0.25% BAC, -0.13+/-0.10, n=7; Buffer, -0.11+/-0.11, n=8). Treatment with 0.25% and 0.5% BAC for 7 days did not further increase light aversion in WT mice (7 day AI: 0.5% BAC, 0.445+/-0.08, n=9, 0.25% BAC, 0.32+/-0.09, n=9). Corneal sensitivity correlated to the level of BAC after 1 day of treatment (WT blink response, n=20 for all: 2% BAC, 0.78+/-0.17; 0.5% BAC, 0.69+/-0.10, 0.25% BAC, 0.52+/-0.10, Buffer, 0.47+/-0.11). WT and OPN4DTA/DTA mice showed no difference in corneal sensitivity. Buffer and 0.25% BAC showing no increased corneal fluorescein staining, a trend to increased staining with 0.5% and significant staining with 2% BAC. OPN4DTA/DTA mice showed the same damage to 2% BAC as WT mice. These studies establish light aversion in a clinically relevant mouse model of photoallodynia. In BAC-treated mice, there is a correlation between corneal surface damage, corneal sensitivity and light aversion. Light aversion is dependent on melanopsin-expressing cells but corneal sensitivity is not, indicating photo- and mechanosensitivity is mediated by different neural circuits. Further investigation of the role of melanopsin expressing cells in specific disease etiologies may provide insights to potential clinical classification and management of photoallodynia. 
RD 9/30/2020