[New concepts on diabetic retinopathy: neural versus vascular damage].

Diabetic retinopathy is the leading cause of irreversible legal blindness in working-age adults. The number of people worldwide at risk of developing vision loss from diabetes is predicted to double over the next 30 years. Some elements suggest that neurodegenerative changes occur beyond vascular damage. These changes include increased apoptosis, glial cell reactivity, microglial activation, and altered glutamate metabolism, and could explain some of the functional abnormalities that begin soon after the onset of diabetes, as early changes in electroretinogram. This review article will present some evidences that point out neurodegeneration as a possible initial event in diabetic retinopathy.

[1]  John Calvin Reed,et al.  Bax is increased in the retina of diabetic subjects and is associated with pericyte apoptosis in vivo and in vitro. , 2000, The American journal of pathology.

[2]  G. Bresnick Diabetic retinopathy viewed as a neurosensory disorder. , 1986, Archives of ophthalmology.

[3]  T. Gardner,et al.  Minocycline reduces proinflammatory cytokine expression, microglial activation, and caspase-3 activation in a rodent model of diabetic retinopathy. , 2005, Diabetes.

[4]  M Palta,et al.  Predicting progression to severe proliferative diabetic retinopathy. , 1987, Archives of ophthalmology.

[5]  T. Gardner,et al.  Diabetic retinopathy: more than meets the eye. , 2002, Survey of ophthalmology.

[6]  S. Mohr,et al.  Caspase activation in retinas of diabetic and galactosemic mice and diabetic patients. , 2002, Diabetes.

[7]  K F LaNoue,et al.  Nitrogen shuttling between neurons and glial cells during glutamate synthesis , 2001, Journal of neurochemistry.

[8]  T. Gardner,et al.  Retinal neurodegeneration: early pathology in diabetes , 2000, Clinical & experimental ophthalmology.

[9]  D. DeMets,et al.  The Wisconsin epidemiologic study of diabetic retinopathy. II. Prevalence and risk of diabetic retinopathy when age at diagnosis is less than 30 years. , 1984, Archives of ophthalmology.

[10]  P. Fort,et al.  Diabetes reduces basal retinal insulin receptor signaling: reversal with systemic and local insulin. , 2006, Diabetes.

[11]  P. Gasque,et al.  "Eat me" and "don't eat me" signals govern the innate immune response and tissue repair in the CNS: emphasis on the critical role of the complement system. , 2003, Molecular immunology.

[12]  A. Barber,et al.  Astrocytes increase barrier properties and ZO-1 expression in retinal vascular endothelial cells. , 1997, Investigative ophthalmology & visual science.

[13]  K. Wellen,et al.  Inflammation, stress, and diabetes. , 2005, The Journal of clinical investigation.

[14]  E. Newman New roles for astrocytes: Regulation of synaptic transmission , 2003, Trends in Neurosciences.

[15]  M. Schneck,et al.  Multifocal electroretinogram and short-wavelength automated perimetry measures in diabetic eyes with little or no retinopathy. , 2004, Archives of ophthalmology.

[16]  H. Hammes,et al.  Nerve Growth Factor Prevents Both Neuroretinal Programmed Cell Death and Capillary Pathology in Experimental Diabetes , 1995, Molecular medicine.

[17]  T. Gardner,et al.  Insulin Rescues Retinal Neurons from Apoptosis by a Phosphatidylinositol 3-Kinase/Akt-mediated Mechanism That Reduces the Activation of Caspase-3* , 2001, The Journal of Biological Chemistry.

[18]  A. Greco,et al.  From functional to microvascular abnormalities in early diabetic retinopathy. , 1997, Diabetes/metabolism reviews.

[19]  G. Seigel,et al.  Inhibition of neuroretinal cell death by insulin-like growth factor-1 and its analogs. , 2000, Molecular vision.

[20]  G. Schmid-Schönbein,et al.  Activated monocytes and granulocytes, capillary nonperfusion, and neovascularization in diabetic retinopathy. , 1991, The American journal of pathology.

[21]  T W Gardner,et al.  Diabetic retinopathy. , 1998, Diabetes care.

[22]  M. Schneck,et al.  Multifocal electroretinogram delays predict sites of subsequent diabetic retinopathy. , 2004, Investigative ophthalmology & visual science.

[23]  A. Heijl,et al.  Visual fields correlate better than visual acuity to severity of diabetic retinopathy , 2005, Diabetologia.

[24]  N. D. Wangsa-Wirawan,et al.  Retinal Oxygen Fundamental and Clinical Aspects , 2003 .

[25]  S. Wild,et al.  Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. , 2004, Diabetes care.

[26]  D. Zack,et al.  TUNEL-positive ganglion cells in human primary open-angle glaucoma. , 1997, Archives of ophthalmology.

[27]  Jens C. Brüning,et al.  The role of insulin receptor signaling in the brain , 2005, Trends in Endocrinology & Metabolism.

[28]  J. Kushner,et al.  Insulin Receptor Substrate 2 Is Essential for Maturation and Survival of Photoreceptor Cells , 2005, The Journal of Neuroscience.

[29]  D. Puro,et al.  Diabetes-induced dysfunction of the glutamate transporter in retinal Müller cells. , 2002, Investigative ophthalmology & visual science.

[30]  T. Peto,et al.  Impairment of visual evoked potentials: an early central manifestation of diabetic neuropathy? , 2002, Diabetes care.

[31]  C. Kahn,et al.  Knockout of insulin and IGF-1 receptors on vascular endothelial cells protects against retinal neovascularization. , 2003, The Journal of clinical investigation.

[32]  J. Cunha-Vaz,et al.  Early breakdown of the blood-retinal barrier in diabetes. , 1975, The British journal of ophthalmology.

[33]  T. Gardner,et al.  Neural apoptosis in the retina during experimental and human diabetes. Early onset and effect of insulin. , 1998, The Journal of clinical investigation.

[34]  R. Klein,et al.  The incidence of vision loss in a diabetic population. , 1988, Ophthalmology.

[35]  E. Chihara Impairment of Protein Synthesis in the Retinal Tissue in Diabetic Rabbits: Secondary Reduction of Fast Axonal Transport , 1981, Journal of neurochemistry.

[36]  Mark Kester,et al.  Diabetic Retinopathy , 2006, Diabetes.

[37]  Margaret A. Johnson,et al.  The distribution of mitochondrial activity in relation to optic nerve structure. , 2002, Archives of ophthalmology.

[38]  L. Fetler,et al.  Neuroscience. Brain under surveillance: the microglia patrol. , 2005, Science.

[39]  V. Greenstein,et al.  Psychophysical evidence for post-receptoral sensitivity loss in diabetics. , 1992, Investigative ophthalmology & visual science.

[40]  Olaf Strauss,et al.  The retinal pigment epithelium in visual function. , 2005, Physiological reviews.

[41]  A. Barber,et al.  A new view of diabetic retinopathy: a neurodegenerative disease of the eye , 2003, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[42]  R. Masland The fundamental plan of the retina , 2001, Nature Neuroscience.

[43]  E. Chihara,et al.  Retinal nerve fiber layer defect as an early manifestation of diabetic retinopathy. , 1993, Ophthalmology.

[44]  L. Bito,et al.  Intraocular fluid dynamics. IV. Intraocular sites of solute utilization and transport as revealed by studies on aphakic eyes. , 1978, Experimental eye research.

[45]  F. Helmchen,et al.  Resting Microglial Cells Are Highly Dynamic Surveillants of Brain Parenchyma in Vivo , 2005, Science.

[46]  M. Schneck,et al.  Local multifocal oscillatory potential abnormalities in diabetes and early diabetic retinopathy. , 2004, Investigative ophthalmology & visual science.

[47]  M. Lorenzi,et al.  Accelerated death of retinal microvascular cells in human and experimental diabetic retinopathy. , 1996, The Journal of clinical investigation.

[48]  T. Gardner,et al.  Retinal angiogenesis in development and disease , 2005, Nature.

[49]  M. Gillies When does neural degeneration occur in diabetic retinopathy? , 2000, Clinical & experimental ophthalmology.

[50]  A. Schousboe,et al.  Distribution of mitochondria within Muller cells – I. Correlation with retinal vascularization in different mammalian species , 1998, Journal of neurocytology.

[51]  A. Caicedo,et al.  Blood-derived macrophages infiltrate the retina and activate Muller glial cells under experimental choroidal neovascularization. , 2005, Experimental eye research.

[52]  V. Parisi,et al.  Visual electrophysiological responses in persons with type 1 diabetes , 2001, Diabetes/metabolism research and reviews.

[53]  S. Ozdek,et al.  Assessment of nerve fiber layer in diabetic patients with scanning laser polarimetry , 2002, Eye.