Anales RANF

Hanan Awad Alkozi @Real Academia Nacional de Farmacia. Spain 54 Figure 3. Scheme of melanopsin pathway through retinal iRGCs to the suprachiasmatic nucleus for photoentrainment, reaching the paraventricular nucleus where it participate in pupillary light reflex. Finally signals reachs the pineal gland where melatonin synthesis is inhibited/activated by the intracellular pathway shown at the bottom of the photo. It is fascinating to think that the eye has much more functions other than image forming vision, and it participates in several physiological roles. In fact, being the first vehicle in regulating the circadian rhythm is of great importance since numerous biological activities follows a circadian manner (68). For instance, several evidence showed that fully blind humans with no light perception suffers from desynchronized circadian processes due to a lack of light input. This leaded to alteration of the pattern of alertness, mood, performance, alteration of core body temperature; which interferes with their social and professional lives even more seriously than the fact of being blind (67, 69). Very recently, melanopsin was detected in other ocular structures than the retina, it was found to be present in the crystalline lens as well as in the cornea (70, 71). Experiments showed that human epithelial crystalline lens reacts differently under light and darkness conditions, melatonin synthesizing enzyme AANAT as well as melatonin levels significantly increased when cells were submitted to total darkness compared to white light. Moreover, experiments done under different wave lengths showed that melatonin was suppressed in response to blue light, corresponding to an action mediated by melanopsin. This action was through phospholipase C (PLC) pathway, similar to melanopsin containing retinal ganglion cells (70). In the cornea, melanopsin expression was detected in the epithelium and near the endothelial surface. Surprisingly, experiments showed no light response in the mentioned study, suggesting a different sensory role for melanopsin in the cornea (71). Although the trigeminal ganglia in the source of most corneal nerve fibers, a different study showed that melanopsin is also expressed in the trigeminal ganglion neurons, and that it responded to light. This is specially interesting since these neurons are a classic pain sensory cells and the ability for light to cause pain is paradoxical, besides the fact that fiber endings in the cornea are specialized to respond to pressure, temperature, and caspaicin. All these findings together opens a new possible role for melanopsin in the cornea (72). 3.1. The impact of melanopsin activation over melatonin synthesis: timing is everything One of the most fascinating facts about melanopsin is its unconscious response to light. Light is an ancient prehistorical phenomena which exists before any living being. Throughout the history, sun light have been a subject of amusement. In numerous cultures and societies sun light was considered as a source of life and nourishment, for example, ancient Egyptians were the first to report beneficial properties from sun exposure 6000 years ago was reported. The Chinese introduced the art of morning sun gaze, and exercises such as yoga or tai chi has strong ties to sunlight (73). These potential benefits of sun