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Victor Perez Fernandez, Morley W John, Cameron Morven; A high-threshold rod input drives retinal dopamine release in response to light.. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2233. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
The origin of light input to dopaminergic amacrine cells of the retina has received significant attention in recent years. However, measurement of dopamine release in the retina in response to light does not correlate with electrophysiological and/or immunohistochemical reports. The purpose of this study was to describe the photoreceptive origin of light-induced dopamine release using transgenic mouse models.
We used UHPLC-MS/MS analysis to quantify DOPAC:DA ratio in the mouse retina in response to 4 light intensities (max 1.6 log W/m2; ~10,000 lux). Wild-type, Gnat2A517G (cone-functionless), and rd/rd (lacking rods and cones) animals were light pulsed and the gap junction blocker meclofenamic acid (MFA) applied intravitreally.
We found that light caused a significant increase in dopamine turnover (DOPAC:DA ratio) in the retinae of both wild-type and Gnat2 A517G mice (p< 0.001; n=3) but only at very bright light intensities (> 0.65 log W/m2; ~1000 lux), with no significant difference between the two groups. In agreement with previous studies, no significant increase was obtained in response to light in rd/rd mice at any light intensity. The gap junction blocker MFA (1mM) caused a significant reduction in light induced dopamine release in both wild-type (p<0.01; n=3) and Gnat2A517G (p<0.05; n=3) animals, but did not completely abolish the light-induced increase in comparison to dark conditions.
We find a surprising role for rods as the primary photoreceptor contributing to light-induced dopamine release in the mouse retina. We have previously shown that light-induced dopamine release in rod-inactivated Gnat1-/- mice was significantly reduced, indicating little cone input to this response. Our data with the Gnat2A517G mice supports this finding, but given that this input has a very high threshold, at least 6 orders of magnitude above the rod threshold, the mechanism of this light gating remains unknown. It is possible that ipRGCs are playing a role in this input, but require a functional rod input to convey this message.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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