Exp Clin Endocrinol Diabetes 2012; 120(04): 199-201
DOI: 10.1055/s-0032-1304571
Mini-Review Series on Diabetes and its Complications
© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Crosstalk in the Retinal Neurovascular Unit – Lessons for the Diabetic Retina

Y. Feng
1   Institute of Experimental and Clinical Pharmacology and Toxicology, Medical Faculty Mannheim, University of Heidelberg, Germany
2   5th Medical Department, Medical Faculty Mannheim, University of Heidelberg, Germany
,
S. Busch
2   5th Medical Department, Medical Faculty Mannheim, University of Heidelberg, Germany
,
N. Gretz
3   Medical Research Center, Medical Faculty Mannheim, University of Heidelberg, Germany
,
S. Hoffmann
3   Medical Research Center, Medical Faculty Mannheim, University of Heidelberg, Germany
,
H.-P. Hammes
2   5th Medical Department, Medical Faculty Mannheim, University of Heidelberg, Germany
› Author Affiliations
Further Information

Publication History

received 20 January 2012
first decision 20 January 2012

accepted 30 January 2012

Publication Date:
08 March 2012 (online)

Abstract

Diabetic retinopathy shares important features with neurodegenerative retinal diseases, including loss of ganglion cells and retinal thinning. The impact on vasoregression and subsequent ischemia-driven changes such as macular edema and proliferative retinopathy are not established. Studies using adult neurodegenerative animal models such as the transgenic TGR(CMV-PKD2(1/703)HA) rat imply early activation of the innate immunity system and the complement system as well as microglia playing a role in the damage of the retinal neurovascular unit.

 
  • References

  • 1 Cheung N, Mitchell P, Wong TY. Diabetic retinopathy. Lancet 376: 124-136
  • 2 Tang J, Kern TS. Inflammation in diabetic retinopathy. Prog Retin Eye Res 30: 343-358
  • 3 Silva PS, Cavallerano JD, Sun JK et al. Effect of systemic medications on onset and progression of diabetic retinopathy. Nat Rev Endocrinol. 6 494–508
  • 4 Antonetti DA, Barber AJ, Bronson SK et al. Diabetic retinopathy: seeing beyond glucose-induced microvascular disease. Diabetes 2006; 55: 2401-2411
  • 5 Hammes HP, Federoff HJ, Brownlee M. Nerve growth factor prevents both neuroretinal programmed cell death and capillary pathology in experimental diabetes. Mol Med 1995; 1: 527-534
  • 6 Aizu Y, Oyanagi K, Hu J et al. Degeneration of retinal neuronal processes and pigment epithelium in the early stage of the streptozotocin-diabetic rats. Neuropathology 2002; 22: 161-170
  • 7 Barber AJ, Lieth E, Khin SA et al. Neural apoptosis in the retina during experimental and human diabetes. Early onset and effect of insulin. J Clin Invest 1998; 102: 783-791
  • 8 Wang Q, Gorbey S, Pfister F et al. Long-term treatment with suberythropoietic Epo is vaso- and neuroprotective in experimental diabetic retinopathy. Cell Physiol Biochem 27: 769-782
  • 9 Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes 2005; 54: 1615-1625
  • 10 Du Y, Miller CM, Kern TS. Hyperglycemia increases mitochondrial superoxide in retina and retinal cells. Free Radic Biol Med 2003; 35: 1491-1499
  • 11 Wang Y, Vom Hagen F, Pfister F et al. Receptor for advanced glycation end product expression in experimental diabetic retinopathy. Ann N Y Acad Sci 2008; 1126: 42-45
  • 12 Hammes HP, Feng Y, Pfister F et al. Diabetic retinopathy: targeting vasoregression. Diabetes. 60 9-16
  • 13 Pannicke T, Iandiev I, Wurm A et al. Diabetes alters osmotic swelling characteristics and membrane conductance of glial cells in rat retina. Diabetes 2006; 55: 633-639
  • 14 Krady JK, Basu A, Allen CM et al. Minocycline reduces proinflammatory cytokine expression, microglial activation, and caspase-3 activation in a rodent model of diabetic retinopathy. Diabetes 2005; 54: 1559-1565
  • 15 McVicar CM, Hamilton R, Colhoun LM et al. Intervention with an erythropoietin-derived peptide protects against neuroglial and vascular degeneration during diabetic retinopathy. Diabetes 60: 2995-3005
  • 16 Gallagher AR, Hoffmann S, Brown N et al. A truncated polycystin-2 protein causes polycystic kidney disease and retinal degeneration in transgenic rats. J Am Soc Nephrol 2006; 17: 2719-2730
  • 17 Feng Y, Wang Y, Stock O et al. Vasoregression linked to neuronal damage in the rat with defect of polycystin-2. PLoS One 2009; 4: e7328
  • 18 Feng Y, Wang Y, Li L et al. Gene expression profiling of vasoregression in the retina – involvement of microglial cells. PLoS One. 6 e16865
  • 19 Hammes HP, Lin J, Wagner P et al. Angiopoietin-2 causes pericyte dropout in the normal retina: evidence for involvement in diabetic retinopathy. Diabetes 2004; 53: 1104-1110
  • 20 Zheng L, Kern TS. Role of nitric oxide, superoxide, peroxynitrite and PARP in diabetic retinopathy. Front Biosci 2009; 14: 3974-3987
  • 21 Li G, Tang J, Du Y et al. Beneficial effects of a novel RAGE inhibitor on early diabetic retinopathy and tactile allodynia. Mol Vis 17: 3156-3165
  • 22 Kumar S, Zhuo L. Longitudinal in vivo imaging of retinal gliosis in a diabetic mouse model. Exp Eye Res 91: 530-536
  • 23 Park SH, Park JW, Park SJ et al. Apoptotic death of photoreceptors in the streptozotocin-induced diabetic rat retina. Diabetologia 2003; 46: 1260-1268
  • 24 Barber AJ, Antonetti DA, Kern TS et al. The Ins2Akita mouse as a model of early retinal complications in diabetes. Invest Ophthalmol Vis Sci 2005; 46: 2210-2218
  • 25 Hammes HP, Lin J, Bretzel RG et al. Upregulation of the vascular endothelial growth factor/vascular endothelial growth factor receptor system in experimental background diabetic retinopathy of the rat. Diabetes 1998; 47: 401-406
  • 26 Kubota S, Ozawa Y, Kurihara T et al. Roles of AMP-Activated Protein Kinase in Diabetes-Induced Retinal Inflammation. Invest Ophthalmol Vis Sci 52: 9142-9148
  • 27 Gaucher D, Chiappore JA, Paques M et al. Microglial changes occur without neural cell death in diabetic retinopathy. Vision Res 2007; 47: 612-623