title: Abnormal Glycogen Storage by Retinal Neurons in Diabetes.
abstract: OBJECTIVE
  It is widely held that neurons of the central nervous system do not store glycogen and that accumulation of the polysaccharide may cause neurodegeneration. Since primary neural injury occurs in diabetic retinopathy, we examined neuronal glycogen status in the retina of streptozotocin-induced diabetic and control rats.
  
  
  METHODS
  Glycogen was localized in eyes of streptozotocin-induced diabetic and control rats using light microscopic histochemistry and electron microscopy, and correlated with immunohistochemical staining for glycogen phosphorylase and phosphorylated glycogen synthase (pGS).
  
  
  RESULTS
  Electron microscopy of 2-month-old diabetic rats (n = 6) showed massive accumulations of glycogen in the perinuclear cytoplasm of many amacrine neurons. In 4-month-old diabetic rats (n = 11), quantification of glycogen-engorged amacrine cells showed a mean of 26 cells/mm of central retina (SD ± 5), compared to 0.5 (SD ± 0.2) in controls (n = 8). Immunohistochemical staining for glycogen phosphorylase revealed strong expression in amacrine and ganglion cells of control retina, and increased staining in cell processes of the inner plexiform layer in diabetic retina. In control retina, the inactive pGS was consistently sequestered within the cell nuclei of all retinal neurons and the retinal pigment epithelium (RPE), but in diabetics nuclear pGS was reduced or lost in all classes of retinal cell except the ganglion cells and cone photoreceptors.
  
  
  CONCLUSIONS
  The present study identifies a large population of retinal neurons that normally utilize glycogen metabolism but show pathologic storage of the polysaccharide during uncontrolled diabetes.
authors.affiliation: The Wellcome-Wolfson Institute for Experimental Medicine School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom.
authors.forename: Tom A
authors.initials: TA
authors.lastname: Gardiner
authors.affiliation: The Wellcome-Wolfson Institute for Experimental Medicine School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Canning
authors.affiliation: Centre for Biomedical Sciences Education, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom.
authors.forename: Nuala
authors.initials: N
authors.lastname: Tipping
authors.affiliation: The Wellcome-Wolfson Institute for Experimental Medicine School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom.
authors.forename: Desmond B
authors.initials: DB
authors.lastname: Archer
authors.affiliation: The Wellcome-Wolfson Institute for Experimental Medicine School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom.
authors.forename: Alan W
authors.initials: AW
authors.lastname: Stitt
mesh_terms: D025042:Amacrine Cells / Q000378:metabolism; D000818:Animals; D003593:Cytoplasm / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism*; D024981:Glycogen Phosphorylase / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008853:Microscopy / Q000379:methods; D051381:Rats; D055351:Retinal Neurons / Q000378:metabolism*
chemical_list: D006003:Glycogen; D024981:Glycogen Phosphorylase