title: Atorvastatin: an efficient step forward in mesenchymal stem cell therapy of diabetic retinopathy.
abstract: Diabetic retinopathy (DR), a leading cause of vision loss and a significant source of morbidity, is the most common ocular complication of prolonged diabetes mellitus. Most therapeutic approaches address DR by preventing or destroying neovasculature; however, this fails to eliminate pathogenic causes. Mesenchymal stem cells (MSCs) are a promising candidate for cell therapy because they have unique regenerative potential and provide an option to manage retinal injuries. Transplantation of MSCs in rats with diabetes induced by streptozocin administration was shown to ameliorate DR. However, the poor viability and homing of MSCs after transplantation may reduce the efficacy of cell therapy. Intravitreal transplantation of MSCs was shown to augment vascular endothelial growth factor (VEGF). More recent studies have found a central role for VEGF in vascular lesion formation in DR and proposed blockage of VEGF as an effective approach to manage DR. Atorvastatin, a 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitor, has been proven to decrease VEGF production of MSCs under hypoxic conditions. It has also been demonstrated that atorvastatin increases the viability of MSCs through the adenosine monophosphate-activated protein kinase-endothelial nitric oxide synthase signaling pathway. There is also evidence that nitric oxide improves homing of MSCs by increasing chemokine-related receptor CXCR4 expression. It could be hypothesized that co-administration of MSCs with atorvastatin may be a significant step forward in development of an efficient MSC therapy of DR through preventing excess VEGF production by MSCs under hypoxic conditions as well as increasing the viability and homing of transplanted MSCs.
authors.affiliation: Razi Drug Research Center, Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Sayeh
authors.initials: S
authors.lastname: Mottaghi
authors.forename: Bagher
authors.initials: B
authors.lastname: Larijani
authors.forename: Ali M
authors.initials: AM
authors.lastname: Sharifi
mesh_terms: D000818:Animals; D000069059:Atorvastatin; D003930:Diabetic Retinopathy / Q000473:pathology / Q000628:therapy*; D005786:Gene Expression Regulation; D015316:Genetic Therapy; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D011758:Pyrroles / Q000008:administration & dosage*; D051381:Rats; D019718:Receptors, CXCR4 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: C527276:CXCR4 protein, human; D006538:Heptanoic Acids; D011758:Pyrroles; D019718:Receptors, CXCR4; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; D000069059:Atorvastatin; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III