Author Index

Advanced glycation end products pericyte loss role 72

receptor 164

tissue damage in diabetes 148 Age-related macular degeneration,

blood-retinal barrier breakdown 28, 29 Angiopoietins

Angiopoietin-2 and pericyte loss role 73, 74 pericyte signaling 198

proliferative diabetic retinopathy role 120 Angiotensin, see Renin-angiotensin system Animal models, see specific animals Arteriole, retinal changes 8

Astrocyte, functional overview 79, 80, 82, 83

Blood-retinal barrier breakdown pathophysiology

endothelial cell proliferation or death 25 pericyte loss 25

tight junction disassembly 25, 26 vascular endothelial growth factor role 25

drug delivery 32 impairing conditions

age-related macular degeneration 28, 29 central serous choroidoretinopathy 31, 32 diabetic retinopathy 28

retinal vein occlusion 30, 31 retinopathy of prematurity 29, 30 surgery 31

uveitis 31 macular edema 26 pericyte role 199, 200

permeability assays electron microscopy 27 Evans blue 27

fluorescein-labeled lectins 27 horseradish peroxidase tracer 27 magnetic resonance imaging 27 optical coherence tomography 27, 28

physiology 21, 22 tight junctions

claudins 24 occludin 23, 24 overview 22, 23

zonula occludens proteins 26 treatment of breakdown

corticosteroids 33, 34

laser photocoagulation 32, 33 mammalian target of rapamycin inhibitors

34

nonsteroidal anti-inflammatory drugs 34

protein kinase C inhibitors 35

tumor necrosis factormonoclonal antibodies 34

vascular endothelial growth factor inhibitors 34

Candesartan, renin-angiotensin system blockade in diabetic retinopathy 150, 152

Capillary occlusion, retinal 9, 10 Cardiovascular risk, diabetic retinopathy and

prediction

clinical implications 211, 212

genetic links 209–211 heart disease 206, 207 mortality 203, 204 pathogenic link 208, 209

research implications 212, 213 retinal venule imaging 207, 208 stroke 204–206

therapeutic implications 212 Cat, diabetes type 1 models 46 CD14 cell

angiogenesis role 184–186 capillary formation role 182–184

CD34 cell

angiogenesis role 184–186

migration impairment in diabetes 182 Central serous choroidoretinopathy, blood-retinal

barrier breakdown 31, 32 Claudins, tight junctions 24

Connective tissue growth factor, proliferative diabetic retinopathy role 120, 121

Corticosteroids, blood-retinal barrier breakdown management 33, 34

Cotton wool spots, retinal 7–8 Dog, diabetes type 1 models 46

Edema macular 26

Müller cell swelling and retinal edema 89–91 retinal 5–7

Electron microscopy, blood-retinal barrier permeability assay 27

Endothelial cell

endothelial cell-to-pericyte ratio 43, 44 leukocyte interactions, see Leukocyte-endothelial

interactions

proliferation or death in blood-retinal barrier breakdown 25

Endothelial precursor cell features 178

types, see CD14 cell, CD34 cell Epigenetics, factors in diabetes 224, 225

Evans blue, blood-retinal barrier permeability assay 27

Exudate, retinal 4–6

Fibroblast growth factor, proliferative diabetic retinopathy role 119

Fructose feeding, retinopathy development in animal models 53

Fundus, morphological changes in diabetic retinopathy 1, 2

Galactose feeding, retinopathy development in animal models 52, 53

Glial cells, see Astrocyte, Microglial cell, Müller cell Glial fibrillary acidic protein, overexpression

in retina 45, 83

Hematopoietic stem cell, see Stem cells Hemorrhage, diabetic retinopathy 4 Hepatocyte growth factor, proliferative diabetic

retinopathy role 119, 120 Hexosamine pathway

pericyte loss 71, 72

tissue damage in diabetes 148, 149

Horseradish peroxidase tracer, blood-retinal barrier permeability assay 27

Hyperglycemic memory, features 224

Insulin-like growth factor-1 angiogenesis role 180, 181 expression regulation 116–118

overexpression models of retinopathy 53 proliferative diabetic retinopathy role 116–118

Intra-retinal microvascular abnormalities, diabetic retinopathy 10, 11, 42

Laser photocoagulation, blood-retinal barrier breakdown management 32, 33

Lesion distribution patterns dynamics 15, 16 individual lesions 14, 15

vision-threatening complications 14 Leukocyte-endothelial interactions

diabetic retina 163–166 transendothelial migration 162, 163

Leukocyte recruitment adhesion molecules 159, 160

integrin-mediated adhesion regulation 160–162 mechanisms 158–160

Loop, retinal lesions 12, 13

Low-density lipoprotein, modification and pericyte loss 72

Macular edema, blood-retinal barrier breakdown 26 Magnetic resonance imaging, blood-retinal barrier

permeability assay 27

Mammalian target of rapamycin, inhibitors for bloodretinal barrier breakdown management 34

Mesenchymal stem cell, see Stem cells Metabolic memory, see Hyperglycemic memory Microaneurysm, diabetic retinopathy 2–4 Microglial cell

activation 82 functional overview 80

Monocyte chemoattractant protein-1 CD14 cell migration 184 CD34 cell migration 182 repair role 181, 182

Mouse

diabetes type 1 models 48 diabetes type 2 models 51, 52

Müller cell activation 81, 82

extracellular matrix deposition role 100, 101 functional overview 80, 81, 83, 98, 99 glutamate metabolism 87, 88

inflammation and angiogenesis role 99, 100 markers 102, 103

neural stem cell characteristics 102–105 neuroprotective role 101, 102 potassium homeostasis role 88, 89 swelling and retinal edema 89–91

transplantation for retinal neuron regeneration barriers 105

prospects 105, 106

vascular leakage and neovascularization role 84–87

Neovascularization animal models 54

morphological features 11, 12 Neural stem cell, see Stem cells

Nonsteroidal anti-inflammatory drugs, blood-retinal barrier breakdown management 34

Occludin, tight junctions 23, 24

Optical coherence tomography, blood-retinal barrier permeability assay 27, 28

Oxidative stress, tissue damage in diabetes 149

Papillopathy, diabetic 13, 14 Pericyte

blood-retinal barrier breakdown and loss 25 cell-cell contacts 64, 65

endothelial cell-to-pericyte ratio 43, 44 function

adult vasculature maintenance 200 blood-brain and blood-retina barriers 199, 200

blood flow regulation 199

blood vessel morphogenesis and stability 196–198

identification 66, 67, 195, 196 intercellular signaling 65, 66 loss in diabetic retinopathy

animal models hyperglycemic models 69 transgenic animals 69, 70

mechanisms

active elimination 73, 74

advanced glycation end products 72 angiopoietin-2 73, 74

hexosamine pathway 71, 72 low-density lipoprotein modification 72 polyol pathway 71

protein kinase C activation 71

unifying biochemical mechanism 72, 73 overview 43, 68, 69

microvascular function 194 morphology and distribution 62, 63 origin and differentiation 61, 62 retinal function

contractility and blood flow regulation 67 vessel formation and stabilization 67, 68

Pigment epithelium-derived factor functional overview 125

plasma levels in diabetes and nephropathy 133–137 sources 126

Spontaneous Diabetic Torii rat studies of diabetic retinopathy 129–131

vascular endothelial growth factor relationship in diabetic retinopathy 126–129

Platelet-derived growth factor overexpression models of retinopathy 53 pericyte signaling 196, 197, 199

proliferative diabetic retinopathy role 118, 119 Polyol pathway

pericyte loss 71

tissue damage in diabetes 148 Protein kinase C

activation and pericyte loss 71

inhibitors for blood-retinal barrier breakdown management 35, 221

tissue damage in diabetes 148

Rat

diabetes type 1 models chemical induction 46, 47 spontaneous induction 47, 48

diabetes type 2 models 49–51

Spontaneous Diabetic Torii rat studies of diabetic retinopathy 129–131

Reduplication, retinal lesions 12, 13 Renin-angiotensin system

blood system 143, 144 history of study 142, 143 ocular system

diabetes features 145, 147 inhibition

animal studies 150–152 clinical trials 152, 221, 222

overview 144, 145

tissue damage role in diabetes 149, 150 tissue localization 146, 147

tissue systems 144

Retinal vein occlusion, blood-retinal barrier breakdown 30, 31

Retinopathy of prematurity, blood-retinal barrier breakdown 29, 30

Stem cells

angiogenesis growth factors 179–182 assays 179

cell lines 174 characteristics

fusion 175, 176 plasticity 175 self-renewal 175

endothelium repair 178, 179 hematopoietic stem cell 177, 178 mesenchymal stem cell 177 neural stem cell 177

niches 174, 175

Stroke, diabetic retinopathy and prediction 204–206 Stromal cell-derived factor 1

angiogenesis role 180

proliferative diabetic retinopathy role 121 Sucrose feeding, retinopathy development in animal

models 53

Systems biology, diabetic retinopathy study prospects 225

Tight junctions components

claudins 24 occludin 23, 24

zonula occludens proteins 26

disassembly in blood-retinal barrier breakdown 25, 26

overview 22, 23

Transforming growth factor- , pericyte signaling 197, 198

Trypsin digest, retinal vascular analysis 45

Tumor necrosis factor- , monoclonal antibodies for blood-retinal barrier breakdown management 34

Uveitis, blood-retinal barrier breakdown 31

Vascular endothelial growth factor angiogenesis role 179, 180 blood-retinal barrier breakdown role 25 expression regulation 112, 113, 125 gene 111

inhibitors

blood-retinal barrier breakdown management 34

clinical trial design 222, 223

diabetic retinopathy management 137, 138 inhibition strategies 113–115

isoforms 111, 112, 124, 125 overexpression models of retinopathy 53

pigment epithelium-derived factor relationship in diabetic retinopathy 126–129

proliferative diabetic retinopathy role 109–116 receptors 112, 114, 115

sources 111

Spontaneous Diabetic Torii rat studies of diabetic retinopathy 129–131

Vascular permeability, see Blood-retinal barrier Venule

changes and cardiovascular disease risks 207, 208 retinal changes 10

Vision

mechanisms of loss in diabetic retinopathy 16, 17 regional retinopathy lesions and loss

distribution 14 types 17

Zebrafish, diabetes type 1 models 49

Zonula occludens proteins, tight junctions 26