There are two major reasons. Previously, melanopsin-expressing, intrinsically photosensitive retinal ganglion cells have been described (Science 295: 1065-1070 and Science 295: 1070-1073). Our paper shows that when the melanopsin gene is ablated, these cells no longer show any intrinsic photosensitivity. Thus, there are 2 important conclusions. First, melanopsin is absolutely required for the intrinsic photosensitivity of these retinal ganglion cells. Second, these cells are truly autonomously light-sensitive, rather than simply receiving signaling about light synaptically (See figure 1 in the paper).

The pupil study provides a clear, simple demonstration of one function of the melanopsin-associated light-detecting system at the whole-animal level. The quantitative analysis of the data also suggests that there may not be other light-detecting systems in the eye besides rods, cones, and the melanopsin-associated system. Previously, cryptochromes have been proposed to be a light-detecting system in the eye. Our experiments do not support this idea.

In addition to the above summary, a simple behavior such as pupil constriction, is fast and accurate, and may represent a very convenient way to study non-image-forming visual functions.

It has been known for many years that visually blind mice (and humans) are able to respond to light for a variety of non-image-forming visual functions such as synchronizing their sleep cycles to ambient light-dark cycles and constricting their pupils to bright light stimuli. David Berson’s group then discovered intrinsically photosensitive ganglion cells in the retina, which is a major surprise, and our group and Berson’s then found that these cells also express melanopsin, a visual-pigment-like protein. By genetic means, the current paper provides direct proof that melanopsin, and therefore the cells expressing it, indeed has an important, measurable physiological function.

We became interested in the possibility of non-rod/non-cone photoreception in the retina when this scientific question was heating up, and were lucky to be able to do the right experiments and make a contribution to the problem.