Photopotentiation of Inner Retinal Photoresponses Affecting the Pupillary Light Reflex in Mice

Abstract

Abstract: : Purpose: Both rod/cone and ganglion cell photoreceptors contribute to the pupillary light response (PLR) of mice. The present study was designed to understand the relative contributions of these two photoreceptor populations to the PLR by studying responses to low level and saturating light exposure. Methods: Wild–type, outer retinal degenerate (rd/rd), melanopsin–mutant (opn4^–/–), and cryptochrome–mutant (mCry1^–/–;mCry2^–/–) mice at age of 6–12 moths were studied. Dark adapted, unanesthetized mice were exposed to strong white and narrow – bandpass wavelength filtered light. Pupillary responses were measured by infrared video pupillometry. Results: In rd/rd mice, the PLR following supersaturating light exposure did not show bleaching, but showed ∼50% paradoxical augmentation. We have termed this increased response photopotentiation. Approximately 10–fold higher light energy was required to elicit photopotentiation than was required to initiate the PLR itself. Potentiation showed wavelength dependence differing from that necessary to elicit the PLR. Potentiation also manifest as persistent constriction under continuous bright illumination: Under bright monochromatic light, pupils remained constricted for full 60s for wavelengths below 500 nm, while wavelengths longer than 500 nm showed progressive dilation. opn4^–/– mice showed no potentiation of pupillary light response at any fluence tested, and showed escape of pupillary constriction under bright light of all wavelengths. mCry1^–/–;mCry2^–/– mice required ∼ 10 – fold higher fluence for photopotentiation than wild–type animals. Conclusions: Photopotentiation is a unique sensory phenomenon associated with the inner retina, and confers upon the PLR resistance to adaptation under continuous bright illumination. It appears to be controlled by a photopigment (or pigment state) with wavelength and intensity dependence different from that initiating the PLR itself. Photopotentiation and maintenance of pupillary constriction are dependent on melanopsin and partially dependent on cryptochrome. Features of photopotentiation are inconsistent with dependence upon a single univariant pigment, and suggests the presence of photopigment(s) with multiple absorption states.

Keywords: pupillary reflex • retina: proximal (bipolar, amacrine, and ganglion cells) • circadian rhythms