Therapeutic targets for diabetic retinopathy : a translational approach

Therapeutic Targets of Diabetic Retinopathy: A Translational Approach offers a consolidated view of this complex disorder by summarizing the latest evidence-based studies and translating their findings into practical, actionable knowledge. This concise resource covers the fundamentals of diabetic retinopathy and diabetic macular edema with an emphasis on basic science and therapeutic targets on the horizon. Ophthalmologists, optometrists, and researchers will find the translational approach to this common eye disorder to be useful in both research and clinical practice settings. Takes a concise yet comprehensive approach to diabetic eye disorders, covering basic science as well as therapeutic agents with both current and future clinical applications. Covers current diagnostic and management guidelines as well developments on the horizon that are likely to improve patient outcomes. Explains the pathophysiological mechanisms of diabetic retinopathy and diabetic macular edema from both a basic and clinical perspective, helping readers seek promising new therapeutic targets. Consolidates today's available information on this timely topic into a single, convenient resource. Front Cover Therapeutic Targets for Diabetic Retinopathy Therapeutic Targets for Diabetic Retinopathy A Translational Approach Copyright Dedication Contents About the authors Preface REFERENCES Acknowledgments 1 - Introduction of Diabetic retinopathy and principles of treatment Epidemiology of diabetes mellitus and diabetic retinopathy Classification, staging, and severity of DR Current management and its limitations for DR, DME, and PDR Control of systemic risk factors Anti-VEGF therapy Corticosteroid therapy Laser photocoagulation Diabetic vitrectomy References 2 - Diabetes-induced metabolic disorders of diabetic retinopathy Hyperglycemia-induced metabolic pathways and therapeutic targets for diabetic retinopathy Polyol pathway activation Increased accumulation of AGEs Hexosamine biosynthetic pathway activation PKC activation Renin–angiotensin–aldosterone system activation Oxidative stress Nitrosative stress Poly(ADP-ribose) polymerase activation Other metabolic alterations in DR Metabolic memory effect on the progression of DR References 3 - Diabetic retinopathy, a neurovascular unit disease Embryonic origins of neurosensory retina and RPE Inner and outer blood–retinal barrier Neurovascular coupling in inner and outer retina Altered neurovascular coupling of inner retina in DR Altered neurovascular coupling of outer retina in DR Compromised intercellular communication and BRB breakdown in DR Pericyte–EC interaction in DR Interdependent vascular, neuronal, and glial cells in diabetic inner retina Interdependent photoreceptor, glia, and RPE in diabetic outer retina Translational study on keeping integrity of inner and outer NVU in diabetic retina References 4 - The pathogenic role of apoptosis in the development of diabetic retinopathy Cell death in the neurovascular unit of the early diabetic retina Apoptosis of retinal vascular pericytes and endothelial cells Apoptosis of retinal neurons and dysfunction of glia cells Protecting the NVU as therapeutic strategy for DRN Antiapoptotic protein BcL-xL to restore vasoregression and attenuate pathological angiogenesis in diabetic retina References 5 - Diabetic retinopathy, a disease with low-grade inflammation Leukocyte adhesion and leukostasis Activation of microglia Inflammatory cytokines and chemokines in diabetic eyes Hypoxia-induced factor-1α Versatile functions of VEGF-A Placental growth factor Intercellular adhesion molecule-1 Monocyte chemotactic protein-1 Tumor necrosis factor-α Interleukin-1β Interleukin-6 Angiopoietin-2 Inflammatory impact on BRB breakdown Anti-inflammation as a therapeutic strategy Innate and adaptive immunity in DR References 6 - Neurodegeneration and microangiopathy in diabetic retina and choroid Distinct pathophysiologic mechanisms in diabetic retinal neurons, glial cells, and vascular cells Diabetic retinal neuronopathy Neuronal dysfunction and cell loss Retinal glial reactivity and microinflammation Altered balance of neurotrophic factors Diabetic retinal microangiopathy Inner BRB breakdown Endothelial glycocalyx loss Outer BRB breakdown Diabetic choroidopathy Potential therapeutic targets in diabetic retina and choroid References 7 - Proliferative diabetic retinopathy, a disease of pathologic angiogenesis and vasculogenesis Angiogenesis and vasculogenesis in physiological and diabetic retina Vascular endothelial growth factor and sprouting angiogenesis Angiopoietin (Ang)/tyrosine kinase with immunoglobulin-like and EGF-like domains (Tie) system interacts with VEGF in sprout ... Pathological angiogenesis in PDR From vasoregression to angiogenesis in PDR progression Crosstalk between inflammation and angiogenesis in NVU during PDR progression Intussusceptive angiogenesis in PDR Translational approach for anti-angiogenesis in PDR Anti-sprouting angiogenesis for PDR and beyond the surface Vasculogenesis deficit in PDR and endothelial progenitor cells–based therapy References 8 - Pathogenesis of diabetic macular edema Overview of diabetic macular edema New DME classification based on anatomic features of fovea Intracellular/cytotoxic edema Cytotoxic edema and dysfunction of Müller cells Drainage dysfunction of RPE cells Extracellular/vasogenic edema Inner and outer BRB breakdown Inflammation and vasogenic DME Inflammation and vasogenic edema Activated inflammatory cells in DME Anti-inflammation for DME treatment Therapeutic strategy for DME References 9 - Treatments for diabetic retinopathy and diabetic macular edema in pipeline Impact of the protocols by DRCR.net on treatment of diabetic retinopathy and diabetic macular edema Targeting VEGF family Development of anti-VEGF treatment Anti-VEGF biosimilars Targeting HIF-1α Targeting VEGFRs VEGFR antibody VEGFR allosteric inhibitor Tyrosine kinase inhibitors for VEGFRs Targeting VEGF coreceptor or auxiliary proteins Targeting neuropilin1/2 Targeting integrin Targeting Ang-2/tyrosine kinase with immunoglobulin-like and EGF-like domains 2 (Tie2) system Targeting Ang-2 Targeting VE-PTP Bispecific drug Other targets Targeting inflammation Corticosteroids Nonsteroid anti-inflammatory drugs Vascular adhesion protein-1 inhibitor Interleukin-6/IL-6 receptor inhibitor Tumor necrosis factor-α inhibitor Minocycline Neuroprotection Erythropoietin ARA290 Somatostatin and brimonidine Drug delivery and durability Port delivery system with ranibizumab Suprachoroidal injection Topical eye drops Oral route Subcutaneous injection High-dose aflibercept Sustained/controlled release Gene therapy to deliver anti-VEGF agents Subthreshold micropulse laser for DME Improvement of pars plana vitrectomy for PDR References 10 - Future perspectives for diabetic retinopathy management Multidisciplinary collaboration for DR care Pharmacological approaches to DM Side effects of glycemic control Hypertension as a systemic risk factor of DR Oxidative stress as a unifying mechanism and key therapeutic target for DR Targeting interactions of oxidative stress with six key metabolic abnormalities Antioxidants for early DR Regulation of apoptotic pathways as therapeutic strategy Peroxisome proliferator-activated receptor γ agonist RAAS blockers Apoptosis repressor with caspase recruitment domain Erythropoietin, a neurotrophic and anti-apoptotic factor Cell-based treatment for DR Gene therapy combined with cell therapy VEGF and non-VEGF signaling pathways as therapeutic targets Ang-2/Tie2 signaling Anti-inflammatory therapy Kallikrein-kinin system Anti-integrin therapy Genetics of DR Application of artificial intelligence in DR Current application of AI in DR Translating AI data from bench to bedside References Index A B C D E F G H I J K L M N O P R S T V W X Z Back Cover