title: Molecular mechanisms of diabetic retinopathy, general preventive strategies, and novel therapeutic targets.
abstract: The growing number of people with diabetes worldwide suggests that diabetic retinopathy (DR) and diabetic macular edema (DME) will continue to be sight threatening factors. The pathogenesis of diabetic retinopathy is a widespread cause of visual impairment in the world and a range of hyperglycemia-linked pathways have been implicated in the initiation and progression of this condition. Despite understanding the polyol pathway flux, activation of protein kinase C (KPC) isoforms, increased hexosamine pathway flux, and increased advanced glycation end-product (AGE) formation, pathogenic mechanisms underlying diabetes induced vision loss are not fully understood. The purpose of this paper is to review molecular mechanisms that regulate cell survival and apoptosis of retinal cells and discuss new and exciting therapeutic targets with comparison to the old and inefficient preventive strategies. This review highlights the recent advancements in understanding hyperglycemia-induced biochemical and molecular alterations, systemic metabolic factors, and aberrant activation of signaling cascades that ultimately lead to activation of a number of transcription factors causing functional and structural damage to retinal cells. It also reviews the established interventions and emerging molecular targets to avert diabetic retinopathy and its associated risk factors.
authors.affiliation: Department of Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Sher Zaman
authors.initials: SZ
authors.lastname: Safi
authors.affiliation: Department of Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Rajes
authors.identifier: 0000-0001-5142-0708
authors.initials: R
authors.lastname: Qvist
authors.affiliation: Department of Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Selva
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Department of Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Kalaivani
authors.identifier: 0000-0002-9569-5014
authors.initials: K
authors.lastname: Batumalaie
authors.affiliation: Department of Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Ikram Shah Bin
authors.initials: IS
authors.lastname: Ismail
mesh_terms: D001766:Blindness / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D002470:Cell Survival; D003930:Diabetic Retinopathy / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008269:Macular Edema / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D011493:Protein Kinase C / Q000378:metabolism; D012307:Risk Factors
chemical_list: D017127:Glycation End Products, Advanced; D011493:Protein Kinase C
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