Role of Rod, Cone and Melanopsin–Containing Retinal Ganglion Cells in Light Detection for Non–Image–Forming Visual Functions

Abstract

Abstract: : Purpose: In mammals, animals lacking rod and cone photoreceptors are still capable of detecting light for a variety of non–image–forming (NIF) visual functions such as circadian photoentrainment, pupillary light reflex (PLR) and direct effects of light on behavior or masking. The intrinsically photosensitive melanopsin–containing retinal ganglion cells (ipRGCs) are important for light reception for NIF functions. Rods, cones and ipRGCs are the only independent photoreceptors in the mammalian retina capable of signaling light information for NIF functions. The contribution of the different photoreceptors differs depending on the NIF function. The question is, what is the specific role of each individual photoreceptor cell in detecting light for the different NIF visual functions. Methods: These studies will be achieved by using behavioral assays such as pupil constriction and activity rhythms in single and double knockout mice that have the rod, cone and melanopsin phototransduction pathways disabled. We will use the melanopsin knockout animals which have the phototransduction pathway disabled in the ipRGCs. For rods and cones, we will use the transducin α–subunit (Gnat1) knockout and the cone cyclic nucleotide gated channel A3–subunit (Cnga3) knockout, both of which are critically involved in the G–protein–coupled cGMP signaling pathway mediating rod–cone phototransduction. Results: In the absence of melanopsin, animals had incomplete PLR and masking responses to light. These results indicated that rods and cones are able to only partially compensate for the absence of melanopsin. Preliminary results with animals that lack rod and ipRGCs phototransduction functions showed that cones alone are not efficient in allowing the animals to photoentrain to an imposed 24 hour light dark cycle. It is known that a small percentage of non melanopsin–containing RGCs do project to NIF visual centers in the brain that are predominantly innervated by melanopsin–containing cells. We are in the process of determining the role of these ganglion cells in relaying rod and cone NIF light information to the brain. Conclusions: These results indicate that rods, cones and melanopsin ipRGCs have distinct and complementary roles in detecting light for NIF visual functions in mammals.

Keywords: circadian rhythms • opsins • pupillary reflex