Anales RANF

Hanan Awad Alkozi @Real Academia Nacional de Farmacia. Spain 56 over the retina by absorbing the harmful UV light (95). Also, ATP release in the aqueous humor would activate P2X receptors in the ciliary body which leads to IOP decrease; in other words, this could be a method of controlling IOP (96). Another study supporting this suggestion was mentioned previously (for more details, see section 2.), where crystalline lens cells responded variably under different light conditions in terms of melatonin synthesis, another important natural component in regulating IOP (70). Another striking fact about melanopsin in the retinal ganglion cells is that light conditions not only regulate its response, but also it regulates melanopsin expression itself. Experiments showed that melanopsin, in addition of being a key participant in photo-entrainment, its expression is also controlled by light conditions, and it increases significantly at night (97). The mechanism and functional implication of the changes of melanopsin expression are still unclear, however, this could explain the higher sensitivity children face when they suffer light at night, based on a study showed that melatonin suppression in children is more sensitive that adults due to light at night (98). As new discoveries are emerging since the discovery of melanopsin, the mutual relationship between both melanopsin and melatonin in the control of ocular physiology is becoming obvious., though more studies are necessary. Indications propose that melatonin may directly modulate the activity of melanopsin containing retinal ganglion cells as these cells express melatonin receptors (99), however most studies are speculative and the actual answer is still unclear. 4. CONCLUSION Melatonin and melanopsin tight bond is out of doubts, and light could become a new era of ocular pharmacology. In this sense, the current review highlighted the most recent discoveries in the eye and ocular pathologies with a special interest over glaucoma disease, being the second leading cause of blindness and giving its complexity in term of the effect of aqueous humor dynamics leading to retinal cells death and the positive effect of melatonin over regulating IOP. Melanopsin presence and activation is crucial during the day to favor melatonin production at night, however, modern life and artificial light are an important factor for harmony between both melatonin and melanopsin. Abreviations: IOP: Intraocular Pressure. AANAT: Aralalkymine N-acetyltransferase. NAS: N-acetylserotonin. HIOMT: Hydroxyindole O-methyltransferase. MT 1-2 : Melatonin receptor 1, 2 NQO2: Quinone reductase 2. AC: Adenylate cyclase. cAMP: Cyclic adenosine mono- phosphate PKA: Protein kinase A. PLC: Phospholipase C. GC: guanylate cyclase. TRP: Transient Receptor Potential Ion Channels. TRPV4: Transient Receptor Potential vanilloid Channel 4. ipRGC: Intrinsically photosensitive retinal ganglion cells. PI(4,5)P2: Phosphatidylinositol 4,5-bisphosphate. IP3: Inositol 1,4,5-triphosphate DAG: Diacylglycerol. SCN: Suprachiasmatic nucleus. ERG: Electroretinogram. ATP: Adenisine triphosphate UV: Ultraviolet 5. REFERENCES 1. Provencio I, Rodriguez IR, Jiang G, Hayes WP, Moreira EF, Rollag MD. A novel human opsin in the inner retina. J Neurosci. 2000;20(2):600-5. 2. Provencio I. The hidden organ in your eyes. Sci Am. 2011;304(5):54-9. 3. Al-Naggar RA, Anil S. Artificial Light at Night and Cancer: Global Study. Asian Pac J Cancer Prev. 2016;17(10):4661-4. 4. Lerner AB, Case JD, Takahashi Y. Isolation of melatonin and 5-methoxyindole-3-acetic acid from bovine pineal glands. J Biol Chem. 1960;235:1992-7. 5. Bergstrom WH, Hakanson DO. Melatonin: the dark force. Adv Pediatr. 1998;45:91-106. 6. Acuna-Castroviejo D, Escames G, Venegas C, Diaz- Casado ME, Lima-Cabello E, Lopez LC, et al. Extrapineal melatonin: sources, regulation, and potential functions. Cell Mol Life Sci. 2014;71(16):2997-3025. 7. Steinlechner S, Baumgartner I, Klante G, Reiter RJ. Melatonin synthesis in the retina and pineal gland of Djungarian hamsters at different times of the year. Neurochem Int. 1995;27(3):245-51. 8. Bubenik GA, Brown GM, Grota LJ. Immunohistochemical localization of melatonin in the rat Harderian gland. J Histochem Cytochem. 1976;24(11):1173-7. 9. Cahill GM, Parsons SE, Besharse JC. Spectral sensitivity of melatonin synthesis suppression in Xenopus eyecups. Vis Neurosci. 1998;15(3):499-502. 10. Haque R, Chong NW, Ali F, Chaurasia SS, Sengupta T, Chun E, et al. Melatonin synthesis in retina: cAMP- dependent transcriptional regulation of chicken arylalkylamine N-acetyltransferase by a CRE-like sequence and a TTATT repeat motif in the proximal promoter. J Neurochem. 2011;119(1):6-17. 11. Reiter RJ, Tan DX, Fuentes-Broto L. Melatonin: a multitasking molecule. Prog Brain Res. 2010;181:127- 51. 12. Chiou GC, Aimoto T, Chiou LY. Melatonergic involvement in diurnal changes of intraocular pressure in rabbit eyes. Ophthalmic Res. 1985;17(6):373-8.