Photoreceptor Cell - Ganglion Cell (non-rod Non-cone) Photoreceptors

Ganglion Cell (non-rod Non-cone) Photoreceptors

A non-rod non-cone photoreceptor in the eyes of mice, which was shown to mediate circadian rhythms, was discovered in 1991 by Foster et al. These neuronal cells, called intrinsically photosensitive retinal ganglion cells (ipRGC), are a small subset (~1–3%) of the retinal ganglion cells located in the inner retina, that is, in front of the rods and cones located in the outer retina. These light sensitive neurons contain a photopigment, melanopsin, which has an absorption peak of the light at a different wavelength (~480 nm) than rods and cones. Beside circadian / behavioral functions, ipRGCs have a role in initiating the pupillary light reflex.

Dennis Dacey with colleagues showed in a species of Old World monkey that giant ganglion cells expressing melanopsin projected to the lateral geniculate nucleus (LGN). Previously only projections to the midbrain (pre-tectal nucleus) and hypothalamus (suprachiasmatic nucleus) had been shown. However a visual role for the receptor was still unsuspected and unproven.

In 2007, Farhan H. Zaidi and colleagues published pioneering work using rodless coneless humans. Current Biology subsequently announced in their 2008 editorial, commentary and despatches to scientists and ophthalmologists, that the non-rod non-cone photoreceptor had been conclusively discovered in humans using landmark experiments on rodless coneless humans by Zaidi and colleagues As had been found in other mammals, the identity of the non-rod non-cone photoreceptor in humans was found to be a ganglion cell in the inner retina. The workers had tracked down patients with rare diseases wiping out classic rod and cone photoreceptor function but preserving ganglion cell function. Despite having no rods or cones the patients continued to exhibit circadian photoentrainment, circadian behavioural patterns, melanopsin suppression, and pupil reactions, with peak spectral sensitivities to environmental and experimental light matching that for the melanopsin photopigment. Their brains could also associate vision with light of this frequency.

In humans the retinal ganglion cell photoreceptor contributes to conscious sight as well as to non-image-forming functions like circadian rhythms, behaviour and pupil reactions. Since these cells respond mostly to blue light, it has been suggested that they have a role in mesopic vision. Zaidi and colleagues' work with rodless coneless human subjects hence also opened the door into image-forming (visual) roles for the ganglion cell photoreceptor. It was discovered that there are parallel pathways for vision – one classic rod and cone-based pathway arising from the outer retina, and the other a rudimentary visual brightness detector pathway arising from the inner retina, which seems to be activated by light before the other. Classic photoreceptors also feed into the novel photoreceptor system, and colour constancy may be an important role as suggested by Foster. The receptor could be instrumental in understanding many diseases including major causes of blindness worldwide like glaucoma, a disease that affects ganglion cells, and the study of the receptor offered potential as a new avenue to explore in trying to find treatments for blindness. It is in these discoveries of the novel photoreceptor in humans and in the receptors role in vision, rather than its non-image-forming functions, where the receptor may have the greatest impact on society as a whole, though the impact of disturbed circadian rhythms is another area of relevance to clinical medicine.

Most work suggests that the peak spectral sensitivity of the receptor is between 460 and 482 nm. Steven Lockley et al. in 2003 showed that 460 nm wavelengths of light suppress melatonin twice as much as longer 555 nm light. However, in more recent work by Farhan Zaidi et al., using rodless coneless humans, it was found that what consciously led to light perception was a very intense 481 nm stimulus; this means that the receptor, in visual terms, enables some rudimentary vision maximally for blue light.