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Shane Alexander Chambers, Marquis Terrell Walker; Characterization of Trpm1 function in mammalian iris constriction. Invest. Ophthalmol. Vis. Sci. 2019;60(9):5266.
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© ARVO (1962-2015); The Authors (2016-present)
In mammals, the retina is the photosensitive tissue that is responsible for the initial capture of light and transduction of the light-induced signals to the brain to drive image and non-image forming behaviors. Pupillary light reflex (PLR) is a bilateral non-image forming visual behavior which involves the constriction of the iris muscle tissue in response to ambient light intensity. A subset of photosensitive retinal ganglion cells provides the principal pathway for all light input to the olivary pretectal nucleus which directs the neuronal input to drive iris constriction. Recently, transient receptor potential melastanin 1 (Trpm1) knockout mice have been shown to have a severe defect in PLR. In the eye, Trpm1 function has only been shown to be necessary for light-driven responses in rod bipolar cells, our results indicate that Trpm1 has an additional role in iridial tissue. We have designed tests to show that the reduced PLR in Trpm1-/- mice is due to a functional loss of the Trpm1 channel in the iris.
We used RT-PCR and immunohistochemistry to demonstrate Trpm1 expression and localization, respectively. We measured the consensual pupillary reflex of control and Trpm1 knockout mice over a range of light intensities. To further test the requirement of Trpm1 in pupil constriction we measured light responses in enucleated eyes of control and Trpm1 knockout mice.
We found that Trpm1-/- mice demonstrate a severe defect in consensual PLR at all light intensities. Trpm1-/- mice under scotopic and photopic intensities only have ~25% and ~50%of the iris constriction measured in controls, respectively. These data suggest that Trpm1 in the eye has additional function downstream of rod bipolar cell activity. RT-PCR and immunohistochemistry results show robust Trpm1 expression in the iris tissue. Tests in enucleated eyes show light-driven constriction independent of CNS input. The light response of the Trpm1-/- eyes was significantly reduced compared to the control eyes and remained consistent with PLR measurements. Pharmacological trials further demonstrate that Trpm1 expression in the eye is required for normal PLR.
Our results indicate that Trpm1 has a novel and necessary role in the PLR of mammals. These results also indicate that Trpm1 function is required in iridial cells for light-driven constriction.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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