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Anna Matynia, Sachin Parikh, Andrew Charles, Michael Gorin; Dry Eye and Headache Mouse Clinical Models of Photophobia. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5089. doi: https://doi.org/.
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Photoallodynia, a clinical problem of increasing concern, is the perception of discomfort or pain in the presence of normal light. Ocular (dry eye injury, albinism), retinal (achromatopsia and cone-dominant degeneration) and central (migraine) disruptions can cause photoallodynia. We aim to establish mouse models of these etiologies using light aversion as an endophenotype of photoallodynia, and ultimately use them to investigate the molecular and neural mechanisms of photoallodynia.
We used our customized light aversion behavioral test to assess photosensitivity in the following: dry eye injury, using mice treated with topically with benzalkonium chloride (BAC); albinism, using Tyrc2J/J mutant and BALB/cJ mice; cone photoreceptor loss, using GNAT2, CNGA3 and H.reddta mutant mice; and migraine, using nitroglycerin (NTG) injection. Tetravisc and atropine were used to investigate the role of corneal nociception and pupil dilation on light aversion, respectively.
Corneal damage from BAC, confirmed by fluorescein staining, results in increased light aversion (2% BAC, n=7) compared to vehicle (buffer, n=7) at 500 Lux. Albino mice (Tyrc2J/J, n=40) show no increased light sensitivity compared to their parental strain with or without pupil dilation. BALB/cJ mice (n=22), an albino strain in a different genetic background, show greater light aversion than Tyrc2J/J, and further accentuation of the response with dilation. Pigmented C57Bl/6J exhibit increased light aversion with increasing illumination whereas pigmented B6A/J mice (n=25) show a constant level of light aversion across illumination range. Light aversion is cone photoreceptor-independent based upon comparisons of models of cone dysfunction (Gnat2-/-, n=6 and Cnga3-/-, n=7) or achromatopsia (H.reddta, n=12) with normal mice of the same strain. Lastly, mice with NTG-induced migraine (n=6) exhibit increased light aversion compared to vehicle controls (n=6).
We have established dry eye injury and NTG-induced migraine models that exhibit increased light aversion. We found that light sensitivity is more affected by genetic background than by pigmentation level. For retinal etiologies, ipRGCs appear to be critical for light aversion but their role in specific photoallodynia models needs to be evaluated. These models provide some of the first clinically relevant models of photoallodynia.
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