Melatonin and diabetic retinopathy


Diabetes is a group of metabolic diseases characterized by high blood sugar.Hyperglycemia is caused by defective insulin secretion, impaired insulin biology, or both.Long-term hyperglycemia leads to chronic damage and dysfunction of various tissues, especially eyes, kidneys, heart, blood vessels and nerves.Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes, are caused by chronic progressive diabetic retinal microvascular leakage and blockage causing a series of fundus lesions, such as micro hemangioma, rigid seepage, lint spot, new blood vessels, vitreous proliferation, macular edema and retinal detachment.DR can be divided into proliferative diabetic retinopathy and non-proliferative diabetic retinopathy based on the presence of abnormal neovascularization from the retina.Its occurrence is related to the type of diabetes, and the course of diabetes is related to the degree of blood glucose control.DR seriously threatens the visual health of patients and is the first blinding disease among working-age people.Melatonin (MT) is one of the hormones secreted by the pineal gland.Its secretion has obvious circadian rhythm, the secretion is inhibited during the day, and the secretion is active at night.MT has strong neuroendocrine immunomodulatory activity and free radical scavenging antioxidant capacity. Studies have shown that melatonin may have a good intervention effect on diabetic retinopathy.The reason why melatonin can interfere with DR starts from the pathogenesis of DR.DR belongs to diabetic microangiopathosis, which is related to many factors such as increased oxidative stress, moderal-low inflammatory response, endoplasmic reticulum stress and autophagy under hyperglycemia.In hyperglycemia, oxidative stress levels can lead to mitochondrial dysfunction, which activates polyol pathway (PP), protein kinase C(PKC), hexosamine pathway (HBP), AGEs and their receptors (AGEs — RAGE) pathways, and thus produces a large number of oxygen free radicals (ROS).In turn, excessive ROS can activate the above four pathways, resulting in positive feedback, and finally attack the retinal tissue structure, resulting in retinopathy.A large number of ROS damage the retina and surrounding blood vessels and nerves, resulting in moderate-low inflammation, which is mainly manifested by infiltration of some inflammatory factors and inflammatory cells, and finally leads to thickening of basement membrane and formation of microvessels, etc.In addition, in diabetic patients, the ability of their cells to use glucose is reduced, and the lack of intracellular nutrients, including glucose hunger and amino acid hunger, leads to the increase of unfolded proteins and misfolded proteins in the er, and induces the er stress to cause cell apoptosis, resulting in tissue damage.In addition, abnormal autophagy can be caused in diabetics, thus affecting normal tissue cells.MT can interfere with DR mainly because it can act on the pathogenesis of DR mentioned above.There are four main points.1. As one of the strongest antioxidants in the body, MT can directly remove hydroxyl free radicals, hydrogen peroxide and lipid peroxide free radicals, etc. In addition, melatonin can up-regulate glutathione in the retina of diabetic rats and maintain catalase activity, indirectly removing ROS.2.MT inhibits NF-κB activation by reducing the expression of various inflammatory factors, such as TNF-α, IL-6, IL-1β, and so on, thereby reducing retinal inflammation and microvascular disorders.3. Studies have shown that MT can alleviate the occurrence of supramretinal endoplasmic reticulum stress in model mice by down-regulating pro-apoptotic proteins and some apoptosis markers.4. Melatonin can regulate acetylase activity and induce autophagy through the mTOR dependent pathway to promote cell survival. In addition, melatonin can regulate AUTOPhagy of DR by activating AMPK to remove excess free radicals and protect the integrity of mitochondrial inner membrane, thus interfering with cell apoptosis.Although MT has been proved to interfere with DR, it is only in the animal experiment stage at present, and there is no clinical experiment to prove that MT has a definite effect on DR.Melatonin can be used as a health care product in China, but due to the uncertain efficacy, it is treated with caution in many countries and regions. Some researchers even believe that taking a high dose of pineal hormone may promote cerebral vasoconstriction and increase the risk of stroke.Therefore, at present, oral melatonin for the treatment of DR is not wise, blood glucose control, lifestyle and evaluation of eye surgery are still the first line of treatment for DR.Wan W W, Long Y, Liu H Z, et al. Correlation between plasma melatonin level and diabetic retinopathy in patients with type 2 diabetes mellitus [J].Progress in Ophthalmology, 201,41(5):447-451. Personal health is a virtue, and spreading health is a merit. If you like my article, please like, forward, and favorites it

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