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1 General aspects (0)   1.1 Epidemiology (0)   1.2 Population genetics (0)   1.3 Pathogenesis (0)   1.4 Quality of life (0)   1.5 Glaucomas as cause of blindness (0)   1.6 Prevention and screening (0) 2 Anatomical structures in glaucoma (0)   2.1 Conjunctiva (0)   2.2 Cornea (0)   2.3 Sclera (0)   2.4 Anterior chamber angle (0)   2.5 Meshwork (0)     2.5.1 Trabecular meshwork (0)     2.5.2 Schlemms canal (0)     2.5.3 Scleral outlet channels (0)   2.6 Aqueous humor dynamics (0)     2.6.1 Production (0)     2.6.2 Outflow (0)       2.6.2.1 Trabecular meshwork (0)       2.6.2.2 Uveoscleral (0)     2.6.3 Compostion (0)   2.7 Episcleral veins and venous pressure (0)   2.8 Iris (0)   2.9 Ciliary body (0)   2.10 Lens (0)   2.11 Vitreous body (0)   2.12 Choroid, peripapillary choroid, peripapillary atrophy (0)   2.13 Retina and retinal nerve fibre layer (0)   2.14 Optic disc (0)   2.15 Optic nerve (0)   2.16 Chiasma and retrochiasmal central nervous system (0)   2.17 Stem cells (0)   2.20 Other (0) 3 Laboratory methods (0)   3.1 Microscopy (0)   3.2 Electron microscopy (0)   3.3 Immunohistochemistry (0)   3.4 Molecular genetics (0)     3.4.1 Linkage studies (0)     3.4.2 Gene studies (0)   3.5 Molecular biology incl. SiRNA (0)   3.6 Cellular biology (0)   3.7 Biochemistry (0)   3.8 Pharmacology (0)   3.9 Pathophysiology (0)   3.10 Immunobiology (0)   3.11 Pharmacogenetics (0)   3.12 Proteomics (0)   3.13 In vivo imaging (0)     3.13.1 Laser Scanning (0)       3.13.1.1 Confocal Scanning Laser Ophthalmoscopy (0)       3.13.1.2 Confocal Scanning Laser Polarimetry (0)     3.13.2 Optical Coherence Tomography (0)       3.13.2.1 Anterior Segment (0)       3.13.2.2 Posterior Segment (0)     3.13.3 RGC Imaging (0)     3.13.4 Other (0)   3.20 Other (0) 4 Tissue culture of ocular cells (0) 5 Experimental glaucoma; animal models (0)   5.1 Rodent (0)   5.2 Primates (0)   5.3 Other (0) 6 Clinical examination methods (0)   6.1 Intraocular pressure measurement; factors affecting IOP (0)     6.1.1 Devices, techniques (0)     6.1.2 Fluctuation, circadian rhythms (0)     6.1.3 Factors affecting IOP (0)   6.2 Tonography, aqueous flow measurement (see also 2.6) (0)   6.3 Biomicroscopy (slitlamp) (0)     6.3.1 Anterior segment (0)     6.3.2 Posterior segment (0)   6.4 Gonioscopy (0)   6.5 Ophthalmoscopy (0)   6.6 Visual field examination and other visual function tests (0)     6.6.1 Conventional manual (0)     6.6.2 Automated (0)     6.6.3 Special methods (e.g. color, contrast, SWAP etc.) (0)   6.7 Electro-ophthalmodiagnosis (0)   6.8 Photography (0)     6.8.1 Anterior segment (0)     6.8.2 Posterior segment (0)   6.9 Computerized image analysis (0)     6.9.1 Laser scanning (0)       6.9.1.1 Confocal Scanning Laser Ophthalmoscopy (0)       6.9.1.2 Confocal Scanning Laser Polarimetry (0)     6.9.2 Optical coherence tomography (0)       6.9.2.1 Anterior (0)       6.9.2.2 Posterior (0)     6.9.5 Other (0)   6.10 Fluorescein (ICG) angiography (0)     6.10.1 Anterior segment (0)     6.10.2 Posterior segment (0)   6.11 Bloodflow measurements (0)   6.12 Ultrasonography and ultrasound biomicroscopy (0)   6.13 Provocative tests (0)   6.19 Telemedicine (0)   6.20 Progression (0)   6.30 Other (0) 8 Refractive errors in relation to glaucoma (0)   8.1 Myopia (0)   8.2 Hypermetropia (0)   8.3 Contact lenses (0)   8.4 Refractive surgical procedures (0)   8.5 Other (0) 9 Clinical forms of glaucomas (0)   9.1 Developmental glaucomas (0)     9.1.1 Congenital glaucoma, Buphthalmos (0)     9.1.2 Juvenile glaucoma (0)     9.1.3 Syndromes of Axenfeld, Rieger, Peters, aniridia (0)     9.1.4 Other (0)   9.2 Primary open angle glaucomas (0)     9.2.1 Ocular hypertension (0)     9.2.2 Other risk factors for glaucoma (0)     9.2.3 Open angle glaucoma with elevated IOP (0)     9.2.4 Normal pressure glaucoma (0)   9.3 Primary angle closure glaucomas (0)     9.3.1 Acute primary angle closure glaucoma (pupillary block) (0)     9.3.2 Chronic primary angle closure glaucoma (pupillary block) (0)     9.3.3 Plateau iris syndrome (0)     9.3.4 Primary angle closure suspect (0)     9.3.5 Primary angle closure (0)     9.3.10 Other (0)   9.4 Glaucomas associated with other ocular and systemic disorders (0)     9.4.1 Steroid-induced glaucoma (0)     9.4.2 Glaucomas associated with disorders of the cornea, conjunctiva, sclera (0)       9.4.2.1 Iridocorneal endothelial syndrome (ICE, incl. irisatrophy) (0)       9.4.2.2 Posterior polymorphous dystrophy (0)       9.4.2.3 Fuchs' endothelial dystrophy (0)       9.4.2.5 Other (0)     9.4.3 Glaucomas associated with disorders of the iris and ciliary body (0)       9.4.3.1 Pigmentary glaucoma (0)       9.4.3.5 Other (0)     9.4.4 Glaucomas associated with disorders of the lens (0)       9.4.4.1 Exfoliation syndrome (0)       9.4.4.2 Glaucomas associated with cataracts (0)       9.4.4.3 Glaucomas associated with lens dislocation (0)       9.4.4.5 Other (0)     9.4.5 Glaucomas associated with disorders of the retina, choroid and vitreous (0)       9.4.5.1 Neovascular glaucoma (0)       9.4.5.5 Other (0)     9.4.6 Glaucomas associated with inflammation, uveitis (0)     9.4.7 Glaucomas associated with ocular trauma (0)     9.4.8 Glaucomas associated with intraocular tumors (0)     9.4.9 Glaucomas associated with elevated episcleral venous pressure (0)       9.4.10 Glaucomas associated with hemorrhage (0)     9.4.11 Glaucomas following intraocular surgery (0)       9.4.11.1 Ciliary block (malignant) glaucoma (0)       9.4.11.2 Glaucomas in aphakia and pseudophakia (0)       9.4.11.3 Epithelial, fibrous, and endothelial proliferation (0)       9.4.11.4 Glaucomas associated with corneal surgery (0)       9.4.11.5 Glaucomas associated with vitreoretinal surgery (0)     9.4.15 Glaucoma in relation to systemic disease (0)     9.4.20 Other (0) 10 Differential diagnosis e.g. anterior and posterior ischemic optic neuropathy (0) 11 Medical treatment (0)   11.1 General management, indication (0)   11.2 Cholinergic drugs (0)   11.3 Adrenergic drugs (0)     11.3.1 Epinephrine (0)     11.3.2 Thymoxamine, dapiprazole (0)     11.3.3 Apraclonidine, brimonidine (0)     11.3.4 Betablocker (0)     11.3.5 Other (0)   11.4 Prostaglandins (0)   11.5 Carbonic anhydrase inhibitors (0)     11.5.1 Systemic (0)     11.5.2 Topical (0)   11.6 Osmotic treatment (0)   11.7 Treatment of bloodflow (0)   11.8 Neuroprotection (0)   11.9 Gene therapy (0)   11.13 Combination therapy (0)     11.13.1 Betablocker and pilocarpine (0)     11.13.2 Betablocker and carbon anhydrase inhibitor (0)     11.13.3 Betablocker and brimonidine (0)     11.13.4 Betablocker and prostaglandin (0)     11.13.5 Other (0)   11.14 Investigational drugs; pharmacological experiments (0)   11.15 Other drugs in relation to glaucoma (0)   11.16 Vehicles, delivery systems, pharmacokinetics, formulation (0)   11.17 Cooperation with medical therapy e.g. persistency, compliance, adherence (0)   11.20 Other (0) 12 Surgical treatment (0)   12.1 General management, indication (0)   12.2 Laser iridotomy (0)   12.3 Laser iridoplasty (0)   12.4 Laser trabeculoplasty and other laser treatment of the angle (0)   12.7 Surgical iridectomy (0)   12.8 Filtering surgery (0)     12.8.1 Without tube implant (0)     12.8.2 With tube implant or other drainage devices (0)     12.8.3 Non-perforating (0)     12.8.4 Using laser (0)     12.8.5 Other (0)     12.8.10 Woundhealing antifibrosis (0)     12.8.11 Complications, endophthalmitis (0)   12.9 Trabeculotomy, goniotomy (0)   12.10 Cyclodestruction (0)   12.11 Cyclodialysis (0)   12.12 Cataract extraction (0)     12.12.1 Intracapsular (0)     12.12.2 Extracapsular (0)     12.12.3 Phacoemulsification (0)   12.14 Combined cataract extraction and glaucoma surgery (0)     12.14.1 Intracapsular (0)     12.14.2 Extracapsular (0)     12.14.3 Phacoemulsification (0)   12.15 Capsulotomy (0)   12.16 Vitrectomy (0)   12.17 Anesthesia (0)   12.20 Other (0) 13 Therapeutic prognosis and outcome (0)   13.1 Prognostic factors (0)   13.2 Outcome (0)     13.2.1 IOP (0)     13.2.2 Visual field (0)       13.2.2.1 Progression (0)       13.2.2.2 Improvement (0)     13.2.3 Other (0) 14 Costing studies; pharmacoeconomics (0) 15 Miscellaneous (745)

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Abstract #109459 Published in IGR 24-1/2

Metformin protects against retinal ischemia/reperfusion injury through AMPK-mediated mitochondrial fusion

Zhang K; Wang T; Sun GF; Xiao JX; Jiang LP; Tou FF; Qu XH; Han XJ
Free Radical Biology and-Medicine 2023; 205: 47-61

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Retinal ischemia/reperfusion (I/R) injury is a common pathological process responsible for cellular damage in glaucoma, diabetic retinopathy and hypertensive retinopathy. Metformin is a biguanide drug that exerts strong effects on multiple diseases. This study aims to evaluate the protective effect of metformin against retinal I/R injury and its underlying mechanism. I/R induced reduction in retina thickness and cell number in ganglion cell layer, and metformin alleviated I/R-induced retinal injury. Both retinal I/R and simulated ischemia/reperfusion (SIR) in R28 cells down-regulated expression of mitochondrial fusion protein Mfn2 and OPA1, which led to mitochondrial fission. Metformin also alleviated damage in R28 cells, and reversed the alteration in Mfn2 and OPA1, mitochondrial fission and mitochondrial membrane potential (MMP) disruption-induced by I/R or SIR as well. Intriguingly, inhibition of AMPK by compound C or siRNA prevented metformin-mediated up-regulation of Mfn2 and OPA1. Compound C and knockdown of Mfn2 or OPA1 dramatically alleviated the protective effect of metformin against intracellular ROS generation, MMP disruption, mitochondrial fission and loss of RGCs in ganglion cell layer induced by SIR or I/R. Moreover, scavenging mitochondrial ROS (mito-ROS) by mito-TEMPO exerted the similar protection against I/R-induced retinal injury or SIR-induced damage in R28 cells as metformin. Our data show for the first time that metformin protects against retinal I/R injury through AMPK-mediated mitochondrial fusion and the decreased mito-ROS generation. These findings might also repurpose metformin as a therapeutic agent for retinal I/R injury.

Institute of Geriatrics, Jiangxi Provincial People's Hospital & the First Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, 330006, PR China; Research Institute of Ophthalmology and Visual Sciences, Affiliated Eye Hospital of Nanchang University, Nanchang, Jiangxi, 330006, PR China; Department of Ophthalmology, Shenzhen People's Hospital & the Second Clinical Medical College of Jinan University, Shenzhen, Guangdong, 518020, PR China.

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Classification:

15 Miscellaneous

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