Anales RANF

Melatonin and melanopsin in the eye: friends or foes? @Real Academia Nacional de Farmacia. Spain 55 exposure were translated to the western world during the 18th century, when light therapy was introduced for lupus vulgaris treatment; a discovery by Niels Finsen (1860- 1904) who was awarded the Nobel Prize in Medicine and Physiology (74, 75). Apart from sunlight, humans have come up with numerous ways to create artificial light along the history. From around 500,000 years ago, evidence showed that Homo erectus started to use fire light in caves. In Greece, bronze lamps were used around 700 B.C (76). Until the nineteenth century, the commonly used artificial light was the wax candle, which in comparison to the current lighting, wax candles had very low intensities and low color temperature; hence they produced a very little effect on the circadian system (77). In 1801, Humphrey Davey discovered the incandescence of an energized conductor, a process put in use by Joseph Swan and Thomas Alva Edison developed the incandescent light bulb (78). Nowadays, electricity has proliferated all around the world, because of its increased efficiency and reduced costs. As a result, in the current modern life, homes and work places lack the complete dark nights, indeed, 2/3 of the population in Europe usually experience nights brighter than under a full moon (79). In addition to all, sine the 1960s, artificial lighting has improved to higher intensities, and they mainly contain short wave length light, correspondent to blue light. The exact wave length which is able to activate melanopsin, and hence alter the natural circadian cycle, leading to some serious pathophysiological consequences (77). Although light has proven benefits, and melanopsin activation by the blue component of either artificial or sunlight is crucial for the whole circadian system, however, studies has shown that timing is very important, and light at night, leading to melanopsin activation and, as a consequence, melatonin suppression, is harmful in many levels. The first evidence of the damaging effect the circadian disruption has, is demonstrated with jet lag; a condition resulted from rapid travel across multiple time zones, resulting in rhythm desynchronization, depressed mood, gastrointestinal complaints and cardiovascular problems (80). Another relevant condition is shift work, a condition affecting around 20% of workers in Europe and the US. Epidemiological studies linked shift-workers to increased risk of developing breast, prostate, colorectal, and endometrial cancers (81-83). All studies highlighting the problem of chronodisruption because of the exposure to artificial light at night resulting in melatonin suppression (77). From the other hand, Can some ocular diseases affect the expression of melanopsin? Hence, can it affect our ability to synchronize the circadian rhythm? Interesting studies indicated that melanopsin is among the first developing photosensitive cells in the mammalian retina (84), moreover, experiments in mice has proven their ability to detect light during embryonic stages (85). However, although they develop first, they have a longer period of proliferation and may be some of the last retinal neurons to die in the course of an organism’s lifetime. They are considered atypical central nervous system neurons, acting both as photoreceptors responding directly to environmental stimuli, as well as standard neurons integrating synaptic input and generating action potentials (86-88). Many studies have raised awareness towards these cells being resistant or less vulnerable to damage and disease compared to conventional RGCs. For instance, studies in some rodent glaucoma model examined the sparing of ipRGCs, suggesting that IOP threshold to damage these cells is much higher than it is in conventional RGCs (86). Different studies indicate melanopsin resistance to damage in optic nerve damage in inherited optic neuropathy, as well as studies indicating that these cells may be resistant to glutamate-induced excitotoxicity (87-90). Little is known about the cellular and molecular mechanisms that provide neuroprotection to these RGCs, however, it appears that along the development of glaucoma, melanopsin cells come to their fate. Different studies showed that melanopsin expressing ganglion cells deteriorated with ocular diseases, resulting in unfavorable outcomes, for example, a study to evaluate melanopsin response in patients with retinitis pigmentosa showed that blue light had a better effect over pupillary response in comparison to red light, however, the effect of short wave length was proportional to the ERG abnormality; patients with non-recordable ERG had significantly reduced response to melanopsin mediated effect “blue light” (91). Another study of melanopsin function in patients with glaucoma demonstrated that melanopsin could be used as an indicator of the progression of this disease, based on clinical evidence that showed that subjects with moderate and severe glaucoma had dysfunctional melanopsin mediated pupillary response in comparison to patients with early stage glaucoma (92). This study supports the facts that melanopsin containing retinal ganglion cells are more resisting to stress during the development of ocular pathologies, moreover, suggesting it as a biomarker to follow up the progressive deterioration noted in glaucoma patients. 3.2. Light, melanopsin, and melatonin: possible therapeutical approach Very recently, an article published by Jesús Pintor was introducing the concept of pharmacology without drugs (93). In this article, the scientist made the following statement: “ Receptor-drug interaction is necessary to obtain a given effect; nevertheless, in some cases, instead of using a chemical messenger or drug it is possible to play with something that surrounds us: light ”. In fact, the blue component of light is the specific agonist for melanopsin receptor, hence, stimulating or inhibiting this receptor could be achieved by means of switching the lights off and/or. This suggestion is based on some published evidence, for instance, in vivo experiments on New Zealand white rabbits showed that light triggered ATP release in the aqueous humor (94). As the crystalline lens is the richest structure in ATP compared to the whole body, it have an important role in the lens by keeping all the active transporters working besides its protective effect