A nonmammalian vertebrate model of blindness reveals functional photoreceptors in the inner retina

Abstract

In mammals, photoreceptors located in the inner retina convey photic information to the brain, regulating diverse non-image-forming tasks such as pupillary light reflexes and photic synchronization (entrainment) of daily activity rhythms. In nonmammalian vertebrates, the retina, deep brain photoreceptors, and pineal organ may be photoreceptive. Here we investigated light perception in the absence of functional cone and rod photoreceptors using GUCY1* chickens, birds carrying a null mutation that causes blindness at hatch. They showed light responses in both the pupillary light reflex and the entrainment of feeding rhythms to a 12:12 h light-dark cycle. Light responses persisted even when the extraretinal photoperception was abolished, but they were lost after enucleation; this strongly indicates the essential role played by the inner retina. A sensitivity spectrum study for the pupillary reflex that combined pupil responses to different monochromatic lights of various intensities demonstrated that a single opsin/vitamin A-based photopigment peaking at 484 nm drives photic responses; the best fit (lowest sum of squares, R(2)=0.9622) was attained with an opsin:vitamin A2 template. The results are the first characterization of functional inner retinal photoreceptors participating in the regulation of non-image-forming activities in nonmammalian vertebrates.