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Published in: Current Diabetes Reports 12/2015

01-12-2015 | Microvascular Complications—Neuropathy (R Pop-Busui, Section Editor)

Retinal Failure in Diabetes: a Feature of Retinal Sensory Neuropathy

Authors: Ellyn J. Gray, Thomas W. Gardner

Published in: Current Diabetes Reports | Issue 12/2015

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Abstract

Physiologic adaptations mediate normal responses to short-term and long-term stresses to ensure organ function. Organ failure results if adaptive responses fail to resolve persistent stresses or maladaptive reactions develop. The retinal neurovascular unit likewise undergoes adaptive responses to diabetes resulting in a retinal sensory neuropathy analogous to other sensory neuropathies. Vision-threatening diabetic retinal neuropathy results from unremitting metabolic and inflammatory stresses, leading to macular edema and proliferative diabetic retinopathy, states of “retinal failure.” Current regulatory strategies focus primarily on the retinal failure stages, but new diagnostic modalities and understanding of the pathophysiology of diabetic retinopathy may facilitate earlier treatment to maintain vision in persons with diabetes.
Literature
1.
go back to reference Grading diabetic retinopathy from stereoscopic color fundus photographs—an extension of the modified Airlie House classification. ETDRS report number 10. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology. 1991;98(5 Suppl):786-806. Grading diabetic retinopathy from stereoscopic color fundus photographs—an extension of the modified Airlie House classification. ETDRS report number 10. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology. 1991;98(5 Suppl):786-806.
2.
3.•
go back to reference Widmaier EP, Raff H, Strang K. Vander’s human physiology: the mechanisms of body function. New York: McGraw-Hill; 2011. Details the general physiologic mechanisms of normal adaptive processes. Widmaier EP, Raff H, Strang K. Vander’s human physiology: the mechanisms of body function. New York: McGraw-Hill; 2011. Details the general physiologic mechanisms of normal adaptive processes.
4.
go back to reference Eaton DC, Pooler JP. Renal functions, basic processes, and anatomy. In: Eaton DC, Pooler JP, editors. Vander’s renal physiology. New York: McGraw-Hill; 2013. p. 1–19. Eaton DC, Pooler JP. Renal functions, basic processes, and anatomy. In: Eaton DC, Pooler JP, editors. Vander’s renal physiology. New York: McGraw-Hill; 2013. p. 1–19.
5.
go back to reference Moreno JA, Radford H, Peretti D et al. Sustained translational repression by eIF2alpha-P mediates prion neurodegeneration. Nature. 2012;485(7399):507–11.PubMedCentralPubMed Moreno JA, Radford H, Peretti D et al. Sustained translational repression by eIF2alpha-P mediates prion neurodegeneration. Nature. 2012;485(7399):507–11.PubMedCentralPubMed
6.
go back to reference Barrett KE, Barman SM, Boitano S et al. Circulation through special regions. In: Barrett KE et al., editors. Ganong’s review of medical physiology. New York: McGraw-Hill; 2012. Barrett KE, Barman SM, Boitano S et al. Circulation through special regions. In: Barrett KE et al., editors. Ganong’s review of medical physiology. New York: McGraw-Hill; 2012.
7.••
go back to reference Pop-Busui R, Herman WH, Feldman EL et al. DCCT and EDIC studies in type 1 diabetes: lessons for diabetic neuropathy regarding metabolic memory and natural history. Curr Diab Rep. 2010;10(4):276–82. Summarizes the major findings from the DCCT/EDIC regarding neuropathy in T1DM.PubMedCentralCrossRefPubMed Pop-Busui R, Herman WH, Feldman EL et al. DCCT and EDIC studies in type 1 diabetes: lessons for diabetic neuropathy regarding metabolic memory and natural history. Curr Diab Rep. 2010;10(4):276–82. Summarizes the major findings from the DCCT/EDIC regarding neuropathy in T1DM.PubMedCentralCrossRefPubMed
8.
go back to reference Bargman JM, Skorecki K. Chronic kidney disease. In: Longo DL et al., editors. Harrison’s principles of internal medicine. New York: McGraw-Hill; 2012. Bargman JM, Skorecki K. Chronic kidney disease. In: Longo DL et al., editors. Harrison’s principles of internal medicine. New York: McGraw-Hill; 2012.
10.
go back to reference Zochodne DW. Mechanisms of diabetic neuron damage: molecular pathways. Handb Clin Neurol. 2014;126:379–99.CrossRefPubMed Zochodne DW. Mechanisms of diabetic neuron damage: molecular pathways. Handb Clin Neurol. 2014;126:379–99.CrossRefPubMed
11.
go back to reference Katirji B, Koontz D. Disorders of peripheral nerves. In: Daroff RB et al., editors. Bradley’s neurology in clinical practice. Philadelphia: Elsevier Saunders; 2012. p. 1977–82. Katirji B, Koontz D. Disorders of peripheral nerves. In: Daroff RB et al., editors. Bradley’s neurology in clinical practice. Philadelphia: Elsevier Saunders; 2012. p. 1977–82.
12.
go back to reference Kennedy JM, Zochodne DW. Impaired peripheral nerve regeneration in diabetes mellitus. J Peripher Nerv Syst. 2005;10:144–57.CrossRefPubMed Kennedy JM, Zochodne DW. Impaired peripheral nerve regeneration in diabetes mellitus. J Peripher Nerv Syst. 2005;10:144–57.CrossRefPubMed
13.
go back to reference Wolter JR. Diabetic retinopathy. Am J Ophthalmol. 1961;51:1123–39.PubMed Wolter JR. Diabetic retinopathy. Am J Ophthalmol. 1961;51:1123–39.PubMed
14.•
go back to reference Callaghan BC, Little AA, Feldman EL et al. Enhanced glucose control for preventing and treating diabetic neuropathy. Cochrane Database Syst Rev. 2012;6:CD007543. A critical review of the effects of glucose control for diabetic neuropathy.PubMedCentralPubMed Callaghan BC, Little AA, Feldman EL et al. Enhanced glucose control for preventing and treating diabetic neuropathy. Cochrane Database Syst Rev. 2012;6:CD007543. A critical review of the effects of glucose control for diabetic neuropathy.PubMedCentralPubMed
15.
go back to reference Calabek B, Callaghan B, Feldman EL. Therapy for diabetic neuropathy: an overview. Handb Clin Neurol. 2014;126:317–33.CrossRefPubMed Calabek B, Callaghan B, Feldman EL. Therapy for diabetic neuropathy: an overview. Handb Clin Neurol. 2014;126:317–33.CrossRefPubMed
16.
go back to reference Petropoulos IN, Green P, Chan AW et al. Corneal confocal microscopy detects neuropathy in patients with type 1 diabetes without retinopathy or microalbuminuria. PLoS One. 2015;10(4), e0123517.PubMedCentralCrossRefPubMed Petropoulos IN, Green P, Chan AW et al. Corneal confocal microscopy detects neuropathy in patients with type 1 diabetes without retinopathy or microalbuminuria. PLoS One. 2015;10(4), e0123517.PubMedCentralCrossRefPubMed
17.
go back to reference Pittasch D, Lobmann R, Behrens-Baumann W et al. Pupil signs of sympathetic autonomic neuropathy in patients with type 1 diabetes. Diabetes Care. 2002;25(9):1545–50.CrossRefPubMed Pittasch D, Lobmann R, Behrens-Baumann W et al. Pupil signs of sympathetic autonomic neuropathy in patients with type 1 diabetes. Diabetes Care. 2002;25(9):1545–50.CrossRefPubMed
19.•
go back to reference Abcouwer SF, Gardner TW. Diabetic retinopathy: loss of neuroretinal adaptation to the diabetic metabolic environment. Ann N Y Acad Sci. 2014;1311:174–90. Summarizes current knowledge of neurovascular adaptations in diabetic retinopathy.PubMedCentralCrossRefPubMed Abcouwer SF, Gardner TW. Diabetic retinopathy: loss of neuroretinal adaptation to the diabetic metabolic environment. Ann N Y Acad Sci. 2014;1311:174–90. Summarizes current knowledge of neurovascular adaptations in diabetic retinopathy.PubMedCentralCrossRefPubMed
20.
go back to reference Kuschinsky W. Neuronal-vascular coupling. A unifying hypothesis. Adv Exp Med Biol. 1997;413:167–76.CrossRefPubMed Kuschinsky W. Neuronal-vascular coupling. A unifying hypothesis. Adv Exp Med Biol. 1997;413:167–76.CrossRefPubMed
21.
22.
go back to reference Kur J, Newman EA, Chan-Ling T. Cellular and physiological mechanisms underlying blood flow regulation in the retina and choroid in health and disease. Prog Retin Eye Res. 2012;31:377–406.PubMedCentralCrossRefPubMed Kur J, Newman EA, Chan-Ling T. Cellular and physiological mechanisms underlying blood flow regulation in the retina and choroid in health and disease. Prog Retin Eye Res. 2012;31:377–406.PubMedCentralCrossRefPubMed
23.
go back to reference Lott ME, Slocomb JE, Shivkumar V et al. Comparison of retinal vasodilator and constrictor responses in type 2 diabetes. Acta Ophthalmol (Copenh). 2012;90(6):e434–41.CrossRef Lott ME, Slocomb JE, Shivkumar V et al. Comparison of retinal vasodilator and constrictor responses in type 2 diabetes. Acta Ophthalmol (Copenh). 2012;90(6):e434–41.CrossRef
24.
go back to reference Garhofer G, Zawinka C, Resch H et al. Reduced response of retinal vessel diameters to flicker stimulation in patients with diabetes. Br J Ophthalmol. 2004;88(7):887–91.PubMedCentralCrossRefPubMed Garhofer G, Zawinka C, Resch H et al. Reduced response of retinal vessel diameters to flicker stimulation in patients with diabetes. Br J Ophthalmol. 2004;88(7):887–91.PubMedCentralCrossRefPubMed
25.
go back to reference Hellgren KJ, Agardh E, Bengtsson B. Progression of early retinal dysfunction in diabetes over time: results of a long-term prospective clinical study. Diabetes. 2014;63(9):3104–11.CrossRefPubMed Hellgren KJ, Agardh E, Bengtsson B. Progression of early retinal dysfunction in diabetes over time: results of a long-term prospective clinical study. Diabetes. 2014;63(9):3104–11.CrossRefPubMed
26.
go back to reference Harrison WW, Bearse MA Jr, Schneck ME et al. Prediction, by retinal location, of the onset of diabetic edema in patients with nonproliferative diabetic retinopathy. Invest Ophthalmol Vis Sci. 2011;52(9):6825–31.PubMedCentralCrossRefPubMed Harrison WW, Bearse MA Jr, Schneck ME et al. Prediction, by retinal location, of the onset of diabetic edema in patients with nonproliferative diabetic retinopathy. Invest Ophthalmol Vis Sci. 2011;52(9):6825–31.PubMedCentralCrossRefPubMed
27.
go back to reference Tzekov R, Arden GB. The electroretinogram in diabetic retinopathy. Surv Ophthalmol. 1999;44(1):53–60.CrossRefPubMed Tzekov R, Arden GB. The electroretinogram in diabetic retinopathy. Surv Ophthalmol. 1999;44(1):53–60.CrossRefPubMed
28.
go back to reference Fort PE, Losiewicz MK, Pennathur S et al. mTORC1-independent reduction of retinal protein synthesis in type 1 diabetes. Diabetes. 2014;63(9):3077–90.PubMedCentralCrossRefPubMed Fort PE, Losiewicz MK, Pennathur S et al. mTORC1-independent reduction of retinal protein synthesis in type 1 diabetes. Diabetes. 2014;63(9):3077–90.PubMedCentralCrossRefPubMed
29.
go back to reference van Guilder HD, Brucklacher RM, Patel K et al. Diabetes downregulates presynaptic proteins and reduces basal synapsin 1 phosphorylation in rat retina. Eur J Neurosci. 2008;28:1–11. van Guilder HD, Brucklacher RM, Patel K et al. Diabetes downregulates presynaptic proteins and reduces basal synapsin 1 phosphorylation in rat retina. Eur J Neurosci. 2008;28:1–11.
30.
go back to reference D’Cruz TS, Weibley BN, Kimball SR et al. Post-translational processing of synaptophysin in the rat retina is disrupted by diabetes. PLoS One. 2012;7(9), e44711.PubMedCentralCrossRefPubMed D’Cruz TS, Weibley BN, Kimball SR et al. Post-translational processing of synaptophysin in the rat retina is disrupted by diabetes. PLoS One. 2012;7(9), e44711.PubMedCentralCrossRefPubMed
31.
go back to reference Barber AJ, Gardner TW, Abcouwer SF. The significance of vascular and neural apoptosis to the pathology of diabetic retinopathy. Invest Ophthalmol Vis Sci. 2011;52(2):1156–63.PubMedCentralCrossRefPubMed Barber AJ, Gardner TW, Abcouwer SF. The significance of vascular and neural apoptosis to the pathology of diabetic retinopathy. Invest Ophthalmol Vis Sci. 2011;52(2):1156–63.PubMedCentralCrossRefPubMed
32.
go back to reference Lasta M, Pemp B, Schmidl D et al. Neurovascular dysfunction precedes neural dysfunction in the retina of patients with type 1 diabetes. Invest Ophthalmol Vis Sci. 2013;54(1):842–7.CrossRefPubMed Lasta M, Pemp B, Schmidl D et al. Neurovascular dysfunction precedes neural dysfunction in the retina of patients with type 1 diabetes. Invest Ophthalmol Vis Sci. 2013;54(1):842–7.CrossRefPubMed
33.
go back to reference Sharma K, Karl B, Mathew AV et al. Metabolomics reveals signature of mitochondrial dysfunction in diabetic kidney disease. J Am Soc Nephrol. 2013;24(11):1901–12.PubMedCentralCrossRefPubMed Sharma K, Karl B, Mathew AV et al. Metabolomics reveals signature of mitochondrial dysfunction in diabetic kidney disease. J Am Soc Nephrol. 2013;24(11):1901–12.PubMedCentralCrossRefPubMed
34.
go back to reference Brosius 3rd FC, He JC. JAK inhibition and progressive kidney disease. Curr Opin Nephrol Hypertens. 2015;24(1):88–95.CrossRefPubMed Brosius 3rd FC, He JC. JAK inhibition and progressive kidney disease. Curr Opin Nephrol Hypertens. 2015;24(1):88–95.CrossRefPubMed
35.
36.
go back to reference Hirsch IB, Brownlee M. Beyond hemoglobin A1c—need for additional markers of risk for diabetic microvascular complications. JAMA. 2010;303(22):2291–2.CrossRefPubMed Hirsch IB, Brownlee M. Beyond hemoglobin A1c—need for additional markers of risk for diabetic microvascular complications. JAMA. 2010;303(22):2291–2.CrossRefPubMed
37.
go back to reference Jackson GR, Scott IU, Quillen DA et al. Inner retinal visual dysfunction is a sensitive marker of non-proliferative diabetic retinopathy. Br J Ophthalmol. 2012;96(5):699–703.CrossRefPubMed Jackson GR, Scott IU, Quillen DA et al. Inner retinal visual dysfunction is a sensitive marker of non-proliferative diabetic retinopathy. Br J Ophthalmol. 2012;96(5):699–703.CrossRefPubMed
38.
go back to reference Gardner TW, Jackson GR. Early detection of neural dysfunction in diabetic retinopathy. In: Guthoff RF, Wiedemann P, editors. Nova Acta Leopoldina. 2014. p. 179–86. Gardner TW, Jackson GR. Early detection of neural dysfunction in diabetic retinopathy. In: Guthoff RF, Wiedemann P, editors. Nova Acta Leopoldina. 2014. p. 179–86.
39.
go back to reference DCCT/EDIC Research Group. Intensive diabetes therapy and ocular surgery in type 1 diabetes. N Engl J Med. 2015;372(18):1722–33.CrossRef DCCT/EDIC Research Group. Intensive diabetes therapy and ocular surgery in type 1 diabetes. N Engl J Med. 2015;372(18):1722–33.CrossRef
40.
go back to reference DCCT/EDIC Research Group. Effect of intensive diabetes therapy on the progression of diabetic retinopathy in patients with type 1 diabetes: 18 years of follow-up in the DCCT/EDIC. Diabetes. 2015;64(2):631–42.CrossRef DCCT/EDIC Research Group. Effect of intensive diabetes therapy on the progression of diabetic retinopathy in patients with type 1 diabetes: 18 years of follow-up in the DCCT/EDIC. Diabetes. 2015;64(2):631–42.CrossRef
Metadata
Title
Retinal Failure in Diabetes: a Feature of Retinal Sensory Neuropathy
Authors
Ellyn J. Gray
Thomas W. Gardner
Publication date
01-12-2015
Publisher
Springer US
Published in
Current Diabetes Reports / Issue 12/2015
Print ISSN: 1534-4827
Electronic ISSN: 1539-0829
DOI
https://doi.org/10.1007/s11892-015-0683-5

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