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Diabetes-induced retinal neurodegeneration occurs before visible microvascular abnormalities. Hyperglycemia-induced endoplasmic reticulum (ER) stress (ERS) and oxidative stress(OS) were considered as the important factors during diabetic retinopathy development. Liraglutide (LIRA), a glucagon-like peptide-1 (GLP-1) analogue, is widely used in the clinic and also proved having protective effect on neurodegenerative diseases. The purpose of this study was to evaluate the neuroprotective effect of LIRA on diabetes-induced retinal neurodegeneration and underlying mechanisms. In vivo, a high-fat diet and streptozotocin (STZ) injection were used inducing diabetes model. Hematoxylin-eosin staining was used for morphological observation and measuring retinal thickness. In vitro, Neuro2a cells were cultured in normal and high-glucose conditions. Flow cytometry was performed to analyze apoptosis. Additionally, Western blotting and Immunohistochemistry were carried out to detect proteins expression. The retinal thickness was decreased in diabetes. However, the retinal thickness reducing was delay after LIRA treatment in diabetes. In vitro, the apoptosis percentage, ROS production and the expression of ERS related protein GRP78, ASK1, p-IRE1α was increased and the expression of Nrf2, p-Erk1/2, Trx was decreased after HG treatment, However, the apoptosis percentage, generation of ROS and the expression of GRP78, ASK1, p-IRE1 were decreased. The expression of Nrf2, p-Erk1/2, Trx was increased significantly after LIRA treatment. Taken together, our results indicated that LIRA can alleviates diabetes-induced retinal neurodegeneration which activated Erk pathway inhibiting OS and regulated the Trx-ASK1complex inhibiting ERS.
This article was published in the following journal.
Name: Neurochemistry international
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A dual inhibitor of both cyclooxygenase and lipoxygenase pathways. It exerts an anti-inflammatory effect by inhibiting the formation of prostaglandins and leukotrienes. The drug also enhances pulmonary hypoxic vasoconstriction and has a protective effect after myocardial ischemia.
Specialized ophthalmic technique used in the surgical repair and or treatment of disorders that include retinal tears or detachment; MACULAR HOLES; hereditary retinal disease; AIDS-related retinal infections; ocular tumors; MACULAR DEGENERATION; DIABETIC RETINOPATHY; and UVEITIS.
Specialized clothing or equipment worn for protection against health hazards. Personal Protective Equipment may include MASKS; RESPIRATORY PROTECTIVE DEVICES; HEAD PROTECTIVE DEVICES; EYE PROTECTIVE DEVICES; EAR PROTECTIVE DEVICES; PROTECTIVE CLOTHING; and protective footwear.
Removal of the whole or part of the vitreous body in treating endophthalmitis, diabetic retinopathy, retinal detachment, intraocular foreign bodies, and some types of glaucoma.
Peripheral, autonomic, and cranial nerve disorders that are associated with DIABETES MELLITUS. These conditions usually result from diabetic microvascular injury involving small blood vessels that supply nerves (VASA NERVORUM). Relatively common conditions which may be associated with diabetic neuropathy include third nerve palsy (see OCULOMOTOR NERVE DISEASES); MONONEUROPATHY; mononeuropathy multiplex; diabetic amyotrophy; a painful POLYNEUROPATHY; autonomic neuropathy; and thoracoabdominal neuropathy. (From Adams et al., Principles of Neurology, 6th ed, p1325)
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