Potential of melatonin to treat or prevent age-related macular degeneration through stimulation of telomerase activity.
Melatonin may play a causal role in the occurrence of age-related macular degeneration (AMD). Replicative capacity and response to injury in the retinal pigment epithelium (RPE) is compromised during aging. Prevention of telomere shortening by antioxidants may be a useful approach for reducing the cumulative effects of oxidative stress in RPE cells. Melatonin, a well known antioxidant, which acts advantageously as an amphiphilic agent, may benefit AMD patients more than commonly used lipophilic or hydrophilic antioxidants. It also may act through mechanisms other than antioxidant mechanisms because melatonin has receptors localized in the RPE, which act locally as a neurohormone and/or neuromodulator. Results of a clinical trial showed that 3mg melatonin given orally each night at bedtime for 3 months to AMD patients reduced pathologic macular changes. I hypothesize that melatonin exerts additional benefit through down-regulating hTERT (catalytic subunit if telomerase) expression and stimulated telomerase activity in RPE, which subsequently helps to prevent or treat AMD. I suggest that melatonin therapy as pharmacologic agents and/or melatonin-rich foods, especially in AMD patients with measured low serum melatonin levels or high risk patients would be possibly an alternative approach to prevent and/or treat AMD. I suggest that melatonin has potential to prevent telomere shortening in RPE, while not precluding other mechanisms, namely antioxidative properties and/or restoration of inner blood-retina barrier (iBRB) integrity, reduced vascular endothelial growth factor (VEGF) and nitric oxide (NO) levels as well as leakage of horseradish peroxidase (HRP), inhibiting hypoxia-inducible factor-1 alpha (HIF-1 alpha) stabilization under hypoxia.
Rastmanesh
Reza
R
Faculty of Nutrition and Food Sciences, Department of Clinical Nutrition and Dietetics, Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran. r.rastmanesh@sbmu.ac.ir
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D008268:Macular Degeneration / Q000188:drug therapy* / Q000201:enzymology; D008550:Melatonin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D055213:Retinal Pigment Epithelium / Q000187:drug effects; D019098:Telomerase / Q000037:antagonists & inhibitors*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D004791:Enzyme Inhibitors; D042461:Vascular Endothelial Growth Factor A; D019098:Telomerase; D008550:Melatonin