Photophobia and abnormally sustained pupil responses in a mouse model of bradyopsia

Abstract

PURPOSE: Mutations in the RGS9 gene cause the visual disorder bradyopsia, which includes difficulty adapting to changes in light and photophobia. The purpose of this study was to determine whether lack of Rgs9 also caused photophobia-like behavior in Rgs9 knockout (Rgs9-/-) mice and to identify useful diagnostic measures of Rgs9 dysfunction. METHODS: We measured two behavioral responses to light and the pupillary light reflex to determine the form and basis of photophobia in Rgs9-/- mice. RESULTS: Rgs9-/- mice spent less time than wild-type mice in both dim and bright light. The mice also showed increased sensitivity to light in negative masking behavior, with a half maximal response at 0.08 lux (0.01 μW·cm(-2)) in Rgs9-/- mice compared to 5.0 lux (0.85 μW·cm(-2)) in wild-type mice. These behaviors were not due to increased anxiety or increased pupil size causing more light to enter the eye. Rather, constriction of the pupil showed that Rgs9-/- mice had an abnormally sustained response to light across multiple irradiance measurement pathways. CONCLUSIONS: Rgs9-/- mice recapitulate a photophobia phenotype of bradyopsia, and the pupil light reflex identifies a simple means to screen for irradiance measurement abnormalities in bradyopsia and potentially other genetic disorders involving photophobia.