- •Preface
- •Contents
- •Contributors
- •1: Living with Diabetic Retinopathy: The Patient’s View
- •My Patient Experience
- •Others’ Experiences
- •Photos of the Meaning of Diabetes
- •References
- •2: Diabetic Retinopathy Screening: Progress or Lack of Progress
- •Definitions of Screening for Diabetic Retinopathy
- •Studies Reporting the Prevalence of Diabetic Retinopathy
- •Reports on Blindness and Visual Impairment
- •Is There Evidence That Treatment for Sight-Threatening Diabetic Retinopathy Is Effective and Agreed Universally?
- •The Evidence That Diabetic Retinopathy Can Be Prevented or the Rate of Deterioration Reduced by Improved Control of Blood Glucose, Blood Pressure and Lipid Levels, and by Giving Up Smoking
- •The Evidence that Laser Treatment Is Effective
- •The Evidence That Vitrectomy for More Advanced Disease Is Effective
- •Progress of Lack of Progress in Screening for Diabetic Retinopathy in Different Parts of the World
- •References
- •3: Functional/Neural Mapping Discoveries in the Diabetic Retina: Advancing Clinical Care with the Multifocal ERG
- •Introduction
- •The Diabetes Epidemic
- •Current Treatment Focus
- •Vasculopathy and Neuropathy of the Retina
- •The Early Efforts
- •Some Breakthroughs
- •Predictive Models of Visible Retinopathy Onset at Specific Locations
- •How Is the mfERG Measured and What is it Measuring?
- •Where Are These Neural Signals Generated in the Retina?
- •Some Key Results
- •Adolescents and Adult Diabetes
- •Type 1 vs. Type 2: Differences in Retinal Function
- •References
- •4: Corneal Diabetic Neuropathy
- •Introduction
- •Corneal Confocal Microscopy
- •Corneal Nerves and Diabetes
- •Conclusion
- •References
- •5: Clinical Phenotypes of Diabetic Retinopathy
- •Natural History
- •MA Formation and Disappearance Rates
- •Alteration of the Blood–Retinal Barrier
- •Retinal Capillary Closure
- •Multimodal Macula Mapping
- •Clinical Retinopathy Phenotypes
- •Relevance for Clinical Trial Design
- •Relevance for Clinical Management
- •Targeted Treatments
- •References
- •6: Visual Psychophysics in Diabetic Retinopathy
- •Introduction
- •Visual Acuity
- •Color Vision
- •Contrast Sensitivity
- •Macular Recovery Function (Nyctometry)
- •Perimetry
- •Microperimetry (Fundus-Related Perimetry)
- •Conclusion
- •References
- •7: Mechanisms of Blood–Retinal Barrier Breakdown in Diabetic Retinopathy
- •The Protective Barriers of the Retina
- •The Inner and the Outer BRB
- •Inflammation and BRB Permeability
- •Leukocyte Mediators of Vascular Leakage
- •Other Mediators of Leukocyte Recruitment in DR
- •Structural Compromise of the BRB
- •Vascular Endothelial Growth Factor
- •Anti-VEGF Properties of Natriuretic Peptides
- •Proposed Model of BRB Breakdown in DR
- •Key Role of AZ in VEGF-Induced Leakage
- •Azurocidin Inhibition Prevents Diabetic Retinal Vascular Leakage
- •References
- •8: Molecular Regulation of Endothelial Cell Tight Junctions and the Blood-Retinal Barrier
- •The Blood-Retinal Barrier
- •The Retinal Vascular Barrier
- •The Junctional Complex
- •ZO Proteins
- •Claudins
- •Junctional Adhesion Molecules
- •Occludin and Tricellulin
- •Vascular Permeability in Diabetic Retinopathy
- •VEGF-Induced Regulation of Endothelial Permeability
- •Occludin Phosphorylation and Permeability
- •Protein Kinase C in Regulation of Barrier Properties
- •Conclusions
- •References
- •9: Capillary Degeneration in Diabetic Retinopathy
- •Vascular Nonperfusion in Diabetes: Mechanisms
- •Molecular Causes of Capillary Degeneration
- •Unexplained Aspects of Diabetes-Induced Degeneration of Retinal Capillaries
- •What Is the Relation Between the Retinal Vasculature and Neuronal Retina Structure and Function in Diabetes?
- •Conclusion
- •References
- •10: Proteases in Diabetic Retinopathy
- •Proteases in Retinal Vasculature
- •Extracellular Proteases
- •Urokinase Plasminogen Activator System (uPA/uPAR System)
- •Matrix Metalloproteinases
- •Endogenous Inhibitors of Proteases
- •Tissue Inhibitors of Metalloproteinases (TIMPs)
- •Plasminogen Activator Inhibitors (PAI)
- •Proteases in Retinal Neovascularization
- •Tissue Inhibitor of Matrix Metalloproteinases in Retinal Neovascularization
- •Inhibition of Retinal Angiogenesis by MMP Inhibitors
- •Inhibition of Retinal Angiogenesis by Inhibitors of the uPA/uPAR System
- •Proteases in Diabetic Macular Edema
- •Conclusion
- •References
- •11: Proteomics in the Vitreous of Diabetic Retinopathy Patients
- •Introduction
- •Vitreous Anatomy
- •A Candidate Approach
- •Proteomic Approaches
- •Vitreous Acquisition
- •Sample Pre-Fractionation
- •Mass Spectrometry
- •Spectral Analysis
- •Data Analysis
- •The Vitreous Proteome
- •2-DE-Based Proteomics
- •1-DE-Based Proteomics
- •Summary and Conclusions
- •References
- •12: Neurodegeneration in Diabetic Retinopathy
- •Introduction
- •Histological Evidence
- •Early Pathology Studies
- •Histological Evidence of Apoptosis
- •Gross Morphological Changes in the Retina
- •Reductions in Numbers of Surviving Amacrine Cells
- •Retinal Ganglion Cell Loss
- •Abnormalities in Ganglion Cell Morphology
- •Centrifugal Axon Abnormalities
- •Nerve Fiber Layer Thickness
- •Biochemical Evidence of Neurodegeneration and Cell Death
- •Functional Evidence of Neurodegenerative Changes
- •Electrophysiological Evidence for Neurodegeneration
- •Optic Nerve Retrograde Transport
- •Other Changes in Visual Function
- •Summary and Conclusions
- •References
- •13: Glucose-Induced Cellular Signaling in Diabetic Retinopathy
- •Introduction
- •Cellular Targets in DR
- •Endothelial Cell (EC) Dysfunction
- •Endothelial-Pericyte Interactions
- •Endothelial-Matrix Interactions
- •Signaling Mechanisms in DR
- •Altered Vasoactive Factors
- •Alteration of Metabolic Pathways
- •Polyol Pathway
- •Hexosamine Pathway
- •Protein Kinase C Pathway
- •Activation of Other Protein Kinases
- •Mitogen-Activated Protein Kinase (MAPK)
- •Increased Oxidative Stress
- •Protein Glycation
- •Aberrant Expression of Growth Factors
- •Transcription Factors
- •Transcription Regulators
- •Concluding Remarks
- •References
- •Introduction
- •The Growth-Hormone/Insulin-Like Growth Factor Pathway in Proliferative Retinopathies
- •Proliferative Diabetic Retinopathy (PDR)
- •Retinopathy of Prematurity (ROP)
- •Animal Models of Proliferative Retinopathies
- •IGFBP-3 as a Regulator of the Growth-Hormone/ Insulin-Like Growth Factor Pathway
- •Conclusion
- •References
- •15: Neurotrophic Factors in Diabetic Retinopathy
- •Diabetic Retinopathy
- •Neurotrophic Factors
- •Neurotrophins and Others
- •Nerve Growth Factor
- •Glial-Cell-Derived Neurotrophic Factor
- •Ciliary Neurotrophic Factor
- •Anti-angiogenic Neurotrophic Factors
- •Pigment-Epithelium-Derived Factor
- •SERPINA3K
- •Brain-Derived Neurotrophic Factor
- •Fibroblast Growth Factors
- •Insulin and Insulin-Like Growth Factor 1
- •Erythropoietin
- •Vascular Endothelial Growth Factor
- •Neurotrophic Factors and the Future of DR Research
- •References
- •16: The Role of CTGF in Diabetic Retinopathy
- •Introduction
- •ECM Remodeling and Wound Healing Mechanisms in Diabetic Retinopathy
- •ECM Remodeling in PCDR
- •Wound Healing Mechanisms in PDR
- •CTGF Structure and Function
- •CTGF in the Eye
- •CTGF in Ocular Fibrosis
- •CTGF in Ocular Angiogenesis
- •CTGF in Diabetic Retinopathy
- •CTGF in BL Thickening in PCDR
- •AGEs and CTGF in BL Thickening in PCDR
- •Role of VEGF in BL Thickening
- •BL Thickening in Diabetic CTGF-Knockout Mice
- •CTGF in PDR
- •Role of CTGF and VEGF in the “Angiofibrotic Switch” in PDR
- •Conclusions
- •References
- •17: Ranibizumab and Other VEGF Antagonists for Diabetic Macular Edema
- •Introduction
- •Pathogenesis of DME and Current Standard of Care
- •Ranibizumab for DME
- •Pegaptanib for DME
- •Bevacizumab for DME
- •VEGF Trap-Eye for DME
- •Other Considerations in the Management of DME
- •Combination Treatment for DME
- •DME and Quality of Life
- •Conclusions
- •References
- •18: Neurodegeneration, Neuropeptides, and Diabetic Retinopathy
- •Introduction
- •Neuropeptides Involved in the Pathogenesis of DR
- •Glutamate
- •Angiotensin II
- •Pigment Epithelial-Derived Factor
- •Somatostatin
- •Erythropoietin
- •Docosahexaenoic Acid and Neuroprotectin D1
- •Brain-Derived Neurotrophic Factor
- •Glial Cell Line-Derived Neurotrophic Factor
- •Ciliary Neurotrophic Factor
- •Adrenomedullin
- •Concluding Remarks and Therapeutic Implications
- •References
- •19: Glial Cell–Derived Cytokines and Vascular Integrity in Diabetic Retinopathy
- •Introduction
- •The BRB Functional Unit Composed of Glial and Endothelial Cells
- •Tight Junctions Between Endothelial Cells Are Substantial Barrier of the BRB
- •Major Cytokines Derived from Glial Cells Affecting Tight Junctions of the BRB
- •VEGF
- •GDNF
- •APKAP12
- •A Possible Treatment of the Retinopathy with Retinoic Acid Analogues
- •Conclusion
- •References
- •20: Impact of Islet Cell Transplantation on Diabetic Retinopathy in Type 1 Diabetes
- •Introduction
- •What Are the Benefits and Risks of Reducing Blood Glucose?
- •On Average, 3 Years Was Required to Demonstrate the Beneficial Effect of Intensive Treatment
- •The Earlier in the Course of Diabetes That Intensive Therapy Is Initiated, Even Before the Onset of Retinopathy, the Greater the Long-Term Benefits
- •Risk Reduction in the Primary Prevention Cohort
- •Risk Reduction in the Secondary Prevention Cohort
- •There Was No Glycemic Threshold Regarding Progression of Retinopathy
- •Diabetic Ketoacidosis (DKA)
- •Efforts to Normalize Blood Glucose Are Associated with Weight Gain in People with Type 1 Diabetes
- •Connecting Peptide (C-Peptide) Responders Have Less Risk of Progression of Retinopathy
- •Effects of Improved Control on Retinopathy Were Sustained in the Long-Term
- •Quality of Life Measure
- •“Metabolic Memory”: A Phenomenon Producing a Long-Term Beneficial Influence of Early Metabolic Control on Clinical Outcomes
- •Need for a More Physiologic Glycemic Control Regimen
- •Effect of Intensive Insulin Therapy on Hypoglycemia Counterregulation
- •b Cell Function
- •Whole Pancreas Transplantation
- •Effect of SPK Transplantation on Diabetic Retinopathy
- •Islet Cell Transplantation
- •Adverse Effects of Chronic Immunosuppression
- •Effect of Islet Cell Transplantation on Retinopathy
- •References
- •Index
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cumulative risk exposure may be significant for patients requiring serial treatment over many years. Therefore, attempts have been made to formulate alternative delivery vehicles for these drugs. Gene therapy and stem cell therapy are new therapeutic strategies that permit us to reduce the frequency of injections, thus reducing local side effects. The use of eyedrops is another potential route of delivery for neurotrophic factors that is currently being explored. However, clinical trials addressed to the evaluation of both the effectiveness and safety of these new treatments in arresting or preventing DR are needed.
Finally, it should be underlined that at present, the milestones in DR treatment are the optimization of blood glucose levels, lowering of blood pressure, and regular fundoscopic screening. Therefore, while we are awaiting the results of clinical research on the use of neuroprotective agents, competent strategies targeting prevention are still required to overcome this disease which is one of the major causes of blindness in the Western world.
REFERENCES
1. Congdom N, Friedman DS, Lietman T. Important causes of visual impairment in the world today. JAMA. 2006;290:2057–60.
2. Mohamed Q, Gillies MC, Wong TY. Management of diabetic retinopathy: a systematic review. JAMA. 2007;298:902–16.
3. Barber AJ. A new view of diabetic retinopathy: a neurodegenerative disease of the eye. Prog Neuropsychopharmacol Biol Psychiatry. 2003;27:283–90.
4. Antonetti DA, Barber AJ, Bronson SK, et al. JDRF Diabetic Retinopathy Center Group. Diabetic retinopathy: seeing beyond glucose-induced microvascular disease. Diabetes. 2006;55:2401–11.
5. Barber AJ, Lieth E, Khin SA, Antonetti DA, Buchanan AG, Gardner TW. Neural apoptosis in the retina during experimental and human diabetes. Early onset and effect of insulin. J Clin Invest. 1988;102:783–91.
6. Lorenzi M, Gerhardinger C. Early cellular and molecular changes induced by diabetes in the retina. Diabetologia. 2001;44:791–804.
7. Asnaghi V, Gerhardinger C, Hoehn T, Adeboje A, Lorenzi M. A role for the polyol pathway in the early neuroretinal apoptosis and glial changes induced by diabetes in the rat. Diabetes. 2003;52:506–11.
8. Carrasco E, Hernandez C, Miralles A, Huguet P, Farrés J, Simó R. Lower somatostatin expression is an early event in diabetic retinopathy and is associated with retinal neurodegeneration. Diabetes Care. 2007;30:2902–8.
9. Carrasco E, Hernández C, de Torres I, Farrés J, Simó R. Lowered cortistatin expression is an early event in the human diabetic retina and is associated with apoptosis and glial activation. Mol Vis. 2008;14:1496–502.
10. Lecleire-Collet A, Tessier LH, Massin P, et al. Advanced glycation end products can induce glial reaction and neuronal degeneration in retinal explants. Br J Ophthalmol. 2005;89: 1631–3.
11. Kern TS, Barber AJ. Retinal ganglion cells in diabetes. J Physiol. 2008;586:4401–8.
12. Park SH, Park JW, Park SJ, et al. Apoptotic death of photoreceptors in the streptozotocininduced diabetic rat retina. Diabetologia. 2003;46:1260–8.
13. Aizu Y, Oyanagi K, Hu J, Nakagawa H. Degeneration of retinal neuronal processes and pigment epithelium in the early stage of the streptozotocin-diabetic rats. Neuropathology. 2002;22:161–70.
320 |
Hernández et al. |
14. Shoham S, Bejar C, Kovalev E, Schorer-Apelbaum D, Weinstock M. Ladostigil prevents gliosis, oxidative-nitrative stress and memory deficits induced by intracerebroventricular injection of streptozotocin in rats. Neuropharmacology. 2007;52:836–43.
15. Cheung AK, Fung MK, Lo AC, et al. Aldose reductase deficiency prevents diabetes-induced blood-retinal barrier breakdown, apoptosis, and glial reactivation in the retina of db/db mice. Diabetes. 2005;54:3119–25.
16. Ng YK, Zeng XX, Ling EA. Expression of glutamate receptors and calcium-binding proteins in the retina of streptozotocin-induced diabetic rats. Brain Res. 2004;1018:66–72.
17. Lieth E, Barber AJ, Xu B, et al. Glial reactivity and impaired glutamate metabolism in short-term experimental diabetic retinopathy. Penn State Retina Research Group. Diabetes. 1998;47:815–20.
18. Li Q, Puro DG. Diabetes-induced dysfunction of the glutamate transporter in retinal Müller cells. Invest Ophthalmol Vis Sci. 2002;43:3109–16.
19. Lieth E, LaNoue KF, Antonetti DA, Ratz M. Diabetes reduces glutamate oxidation and glutamine synthesis in the retina. The Penn State Retina Research Group. Exp Eye Res. 2000;70:723–30.
20. Wilkinson-Berka JL. Angiotensin and diabetic retinopathy. Int J Biochem Cell Biol. 2006; 38:752–65.
21. Chaturvedi N, Porta M, Klein R, et al. DIRECT Programme Study Group. Effect of candesartan on prevention (DIRECT-Prevent 1) and progression (DIRECT-Protect 1) of retinopathy in type 1 diabetes: randomised, placebo-controlled trials. Lancet. 2008;372:1394–402.
22. Sjølie AK, Klein R, Porta M, et al. DIRECT Programme Study Group. Effect of candesartan on progression and regression of retinopathy in type 2 diabetes (DIRECT-Protect 2): a randomised placebo-controlled trial. Lancet. 2008;372:1385–93.
23. Mauer M, Zinman B, Gardiner R, et al. Renal and retinal effects of enalapril and losartan in type 1 diabetes. N Engl J Med. 2009;361:40–51.
24. Chen P, Scicli GM, Guo M, et al. Role of angiotensin II in retinal leukostasis in the diabetic rat. Exp Eye Res. 2006;83:1041–51.
25. Krikov M, Thone-Reineke C, Müller S, Villringer A, Unger T. Candesartan but not ramipril pretreatment improves outcome after stroke and stimulates neurotrophin BNDF/TrkB system in rats. J Hypertens. 2008;26:544–52.
26. Kurihara T, Ozawa Y, Nagai N, et al. Angiotensin II type 1 receptor signaling contributes to synaptophysin degradation and neuronal dysfunction in the diabetic retina. Diabetes. 2008;57:2191–8.
27. Downie LE, Pianta MJ, Vingrys AJ, Wilkinson-Berka JL, Fletcher EL. AT1 receptor inhibition prevents astrocyte degeneration and restores vascular growth in oxygen-induced retinopathy. Glia. 2008;56:1076–90.
28. Silva KC, Rosales MA, Biswas SK, Lopes de Faria JB, Lopes de Faria JM. Diabetic retinal neurodegeneration is associated with mitochondrial oxidative stress and is improved by angiotensin receptor blocker in a model that combines hypertension and diabetes. Diabetes. 2009;58:1382–90.
29. Barnstable CJ, Tombran-Tink J. Neuroprotective and antiangiogenic actions of PEDF in the eye: molecular targets and therapeutic potential. Prog Retin Eye Res. 2004;23:561–77.
30. Dawson DW, Volpert OV, Gillis P, et al. Pigment epithelium derived factor: a potent inhibitor of angiogenesis. Science. 1999;285:245–8.
31. Notari L, Baladron V, Aroca-Aguilar JD, et al. Identification of a lipase-linked cell-membrane receptor for pigment epithelium-derived factor (PEDF). J Biol Chem. 2006;281:38022–37.
32. Filleur S, Nelius T, de Riese W, Kennedy RC. Characterization of PEDF: a multi-functional serpin family protein. J Cell Biochem. 2009;106:769–75.
Neurodegeneration, Neuropeptides, and Diabetic Retinopathy |
321 |
33. Tombran-Tink J, Lara N, Apricio SE, et al. Retinoic acid and dexamethasone regulate the expression of PEDF in retinal and endothelial cells. Exp Eye Res. 2004;78:945–55.
34. Cervia D, Casini G, Bagnoli P. Physiology and pathology of somatostatin in the mammalian retina: a current view. Mol Cell Endocrinol. 2008;286:112–22.
35. Simó R, Lecube A, Sararols L, et al. Deficit of somatostatin-like immunoreactivity in the vitreous fluid of diabetic patients: possible role in the development of proliferative diabetic retinopathy. Diabetes Care. 2002;25:2282–6.
36. Hernández C, Carrasco E, Casamitjana R, Deulofeu R, García-Arumí J, Simó R. Somatostatin molecular variants in the vitreous fluid: a comparative study between diabetic patients with proliferative diabetic retinopathy and nondiabetic control subjects. Diabetes Care. 2005;28:1941–7.
37. Lambooij AC, Kuijpers RW, van Lichtenauer-Kaligis EG, Kliffen M, Baarsma GS, van Hagen PM, et al. Somatostatin receptor 2A expression in choroidal neovascularization secondary to age-related macular degeneration. Invest Ophthalmol Vis Sci. 2000;41:2329–35.
38. Klisovic DD, O’Dorisio MS, Katz SE, et al. Somatostatin receptor gene expression in human ocular tissues: RT-PCR and immunohistochemical study. Invest Ophthalmol Vis Sci. 2001;42:2193–201.
39. Davis MI, Wilson SH, Grant MB. The therapeutic problem of proliferative diabetic retinopathy: targeting somatostatin receptors. Horm Metab Res. 2001;33:295–9.
40. Simó R, Carrasco E, Fonollosa A, García-Arumí J, Casamitjana R, Hernández C. Deficit of somatostatin in the vitreous fluid of patients with diabetic macular edema. Diabetes Care. 2007;30:725–7.
41. Hernández C, Simó R. Strategies for blocking angiogenesis in diabetic retinopathy by intravitreal therapy. From basic science to clinical practice. Expert Opin Investig Drugs. 2007;16:1209–26.
42. Marti HH. Erythropoietin and the hypoxic brain. J Exp Biol. 2004;207:3233–42.
43. Hernández C, Fonollosa A, García-Ramírez M, et al. Erythropoietin is expressed in the human retina and it is highly elevated in the vitreous fluid of patients with diabetic macular edema. Diabetes Care. 2006;29:2028–33.
44. García-Ramírez M, Hernández C, Simó R. Expression of erythropoietin and its receptor in the human retina: a comparative study of diabetic and nondiabetic subjects. Diabetes Care. 2008;31:1189–94.
45. Jelkmann W. Effects of erythropoietin on brain function. Curr Pharm Biotechnol. 2005; 6:65–79.
46. Becerra SP, Amaral J. Erythropoietin: an endogenous retinal survival factor. N Engl J Med. 2002;347:1968–70.
47. Katsura Y, Okano T, Matsuno K, et al. Erythropoietin is highly elevated in vitreous fluid of patients with proliferative diabetic retinopathy. Diabetes Care. 2005;28:2252–4.
48. Watanabe D, Suzuma K, Matsui S, et al. Erythropoietin as a retinal angiogenic factor in proliferative diabetic retinopathy. N Engl J Med. 2005;353:782–92.
49. Inomata Y, Hirata A, Takahashi E, Kawaji T, Fukushima M, Tanihara H. Elevated erythropoietin in vitreous with ischemic retinal diseases. Neuroreport. 2004;15:877–9.
50. Jaquet K, Krause K, Tawakol-Khodai M, Geidel S, Kuck KH. Erythropoietin and VEGF exhibit equal angiogenic potential. Microvasc Res. 2002;64:326–33.
51. García-Arumí J, Fonollosa A, Macià C, et al. Vitreous levels of erythropoietin in patients with macular oedema secondary to retinal vein occlusions: a comparative study with diabetic macular oedema. Eye. 2009;23:1066–71.
52. Chen J, Connor KM, Aderman CM, Smith LE. Erythropoietin deficiency decreases vascular stability in mice. J Clin Invest. 2008;118:526–33.
322 |
Hernández et al. |
53. Zhang J, Wu Y, Jin Y, et al. Intravitreal injection of erythropoietin protects both retinal vascular and neuronal cells in early diabetes. Invest Ophthalmol Vis Sci. 2008;49:732–42.
54. Grant MB, Boulton ME, Ljubimov AV. Erythropoietin: when liability becomes asset in neurovascular repair. J Clin Invest. 2008;118:467–70.
55. Bazan NG, Gordon WC, Rodriguez de Turco EB. Docosahexaenoic acid uptake and metabolism in photoreceptors: retinal conservation by an efficient retinal pigment epithelial cellmediated recycling process. Neurobiol Essent Fatty Acids. 1992;318:295–306.
56. Mukherjee PK, Marcheselli VL, Serhan CN, Bazan NG. Neuroprotectin D1: a docosahexaenoic acid-derived docosatriene protects human retinal pigment epithelial cells from oxidative stress. Proc Natl Acad Sci USA. 2004;101:8491–6.
57. Bazan NG. Neurotrophins induce neuroprotective signaling in the retinal pigment epithelial cell by activating the synthesis of the anti-inflammatory and antiapoptotic neuroprotectin-1. Adv Exp Med Biol. 2008;613:39–44.
58. Seki M, Nawa H, Fukuchi T, Abe H, Takei N. BDNF is upregulated by postnatal development and visual experience: quantitative and immunohistochemical analyses of BDNF in the rat retina. Invest Ophthalmol Vis Sci. 2003;44:3211–8.
59. Seki M, Tanaka T, Sakai Y, et al. Müller cells as a source of brain-derived neurotrophic factor in the retina: noradrenaline upregulates brain-derived neurotrophic factor levels in cultured rat Müller cells. Neurochem Res. 2005;30:1163–70.
60. Kido N, Tanihara H, Honjo M, et al. Neuroprotective effects of brain-derived neurotrophic factor in eyes with NMDA-induced neuronal death. Brain Res. 2000;884:59–67.
61. Cellerino A, Pinzón-Duarte G, Carroll P, Kohler K. Brain-derived neurotrophic factor modulates the development of the dopaminergic network in the rodent retina. J Neurosci. 1998;18:3351–62.
62. Seki M, Tanaka T, Nawa H, et al. Involvement of brain-derived neurotrophic factor in early retinal neuropathy of streptozotocin-induced diabetes in rats: therapeutic potential of brainderived neurotrophic factor for dopaminergic amacrine cells. Diabetes. 2004;53:2412–9.
63. Lin LF, Doherty DH, Lile JD, Bektesh S, Collins F. GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science. 1993;260:1130–2.
64. Sariola H, Saarma M. Novel functions and signalling pathways for GDNF. J Cell Sci. 2003;116:3855–62.
65. Karlsson M, Lindqvist N, Mayordomo R, Hallböök F. Overlapping and specific patterns of GDNF, c-ret and GFR alpha mRNA expression in the developing chicken retina. Mech Dev. 2002;114:161–5.
66. Harada T, Harada C, Mitamura Y, et al. Neurotrophic factor receptors in epiretinal membranes after human diabetic retinopathy. Diabetes Care. 2002;25:1060–5.
67. Nishikiori N, Mitamura Y, Tashimo A, et al. Glial cell line-derived neurotrophic factor in the vitreous of patients with proliferative diabetic retinopathy. Diabetes Care. 2005;28:2588.
68. Stahl N, Yancopoulos GD. The tripartite CNTF receptor complex: activation and signaling involves components shared with other cytokines. J Neurobiol. 1994;25:1454–66.
69. Peterson WM, Wang Q, Tzekova R, Wiegand SJ. Ciliary neurotrophic factor and stress stimuli activate the Jak-STAT pathway in retinal neurons and glia. J Neurosci. 2000;20:4081–90.
70. Beltran WA, Rohrer H, Aguirre GD. Immunolocalization of ciliary neurotrophic factor receptor alpha (CNTFR alpha) in mammalian photoreceptor cells. Mol Vis. 2005;11:232–44.
71. Aizu Y, Katayama H, Takahama S, Hu J, Nakagawa H, Oyanagi K. Topical instillation of ciliary neurotrophic factor inhibits retinal degeneration in streptozotocin-induced diabetic rats. Neuroreport. 2003;14:2067–71.
Neurodegeneration, Neuropeptides, and Diabetic Retinopathy |
323 |
72. Miyashita K, Itoh H, Arai H, et al. The neuroprotective and vasculo-neuro-regenerative roles of adrenomedullin in ischemic brain and its therapeutic potential. Endocrinology. 2006;147:1642–53.
73. Xia CF, Yin H, Borlongan CV, Chao J, Chao L. Adrenomedullin gene delivery protects against cerebral ischemic injury by promoting astrocyte migration and survival. Hum Gene Ther. 2004;15:1243–54.
74. Thiersch M, Raffelsberger W, Frigg R, et al. Analysis of the retinal gene expression profile after hypoxic preconditioning identifies candidate genes for neuroprotection. BMC Genomics. 2008;9:73.