RT Journal Article
A1 Vigh, Jozsef
A1 Tooker, Ryan
A1 Maverick, Emily
T1 Endogenous opioid signaling in the mouse retina modulates pupillary light reflex
JF Investigative Ophthalmology & Visual Science
JO Invest. Ophthalmol. Vis. Sci.
YR 2015
VO 56
IS 7 
SP 5565
OP 5565
SN 1552-5783
AB  In the adult mouse retina, the opioid peptide b-endorphin is expressed by cholinergic amacrine cells (Gallagher et al., 2010). Our data shows that melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs) express b-endorphin-preferring, m-opioid receptors (MORs) and MOR selective agonists strongly attenuate light-evoked firing of ipRGCs. The objective of the present study was to elucidate if opioids, endogenous or exogenous, modulate pupillary light reflex (PLR) via MORs expressed by ipRGCs.<br /> The MOR selective agonist DAMGO (1 mg/ml), or antagonist CTAP (1 mg/ml) was administered via unilateral intravitreal injection (1-2 ml/eye). Contralateral PLR was recorded at 30 frames/s in response to rod-saturating green (1010 photons/cm2/s at 525 nm), dim photopic red (1012 photons/cm2/s at 660 nm) and bright blue (1014 photons/cm2/s at 470 nm) stimuli delivered for 2 min at 2 Hz to the treated eye of mice lightly anesthetized with isoflurane, 30-60 min following intraocular injections. PLR was calculated as percent change relative to the average of control and recovery pupil sizes with NIH Image J.<br /> DAMGO eliminated contralateral PLR evoked by green and red light with intensities below melanopsin activation threshold stimulation but not that evoked by bright blue photopic irradiance that activated melanopsin signaling. Nonetheless, detailed analysis revealed that DAMGO markedly slowed the bright blue light evoked PLR. CTAP slightly enhanced green and red light evoked PLR but not that evoked by our blue stimulus. Similarly, green and red light evoked PLR appeared to be enhanced in MORKO mice but not that evoked by bright blue light.<br /> Our results suggest that endogenous opioid signaling in the retina contributes to the regulation of PLR. The slowing of bright blue light evoked PLR by DAMGO is consistent with the observation that systemically applied opioids accumulate in the vitreous and opiate-dependent patients have slow PLR. <br /> 
RD 10/29/2020