title: The effect of hyperglycemia on hypoperfusion-induced injury.
abstract: Purpose. Because of differences in energy metabolism between the brain and retina, the hypothesis for the study was that, in a model of ocular and cerebral hypoperfusion, the retina would be protected by short-term hyperglycemia, whereas brain injury would be exacerbated. Methods. Hyperglycemia was induced by intraperitoneal streptozotocin. An initial experiment determined the effect of hyperglycemia alone in sham-surgery rats. Simultaneous retinal and cerebral hypoperfusion was achieved by two-vessel occlusion (2VO; permanent ligation of both common carotid arteries). Hyperglycemia was induced 3 days before 2VO by streptozotocin injection. The rats were killed 7 days after 2VO or sham surgery. The retina of one eye was collected for histology/immunohistochemistry and the fellow retina was collected for real-time RT-PCR. The retinas were analyzed for neuronal and glial markers and heat shock protein-27. The brains were processed for histology and immunohistochemistry. Results. Short-term (approximately 10 days) hyperglycemia alone caused no discernible injury to the retina. The retinas of the normoglycemic 2VO animals showed a marked loss of retinal ganglion cells and horizontal cells, thinning of the inner retina, glial cell activation, and infiltration of macrophages. The hyperglycemic 2VO rats displayed remarkable protection of the retinal structure and reduced glial cell activation compared with the normoglycemic 2VO animals. There was a significantly greater number of heat shock protein-27-positive retinal ganglion cells in the normoglycemic animals than in the hyperglycemic ones. Brains of both the normoglycemic and hyperglycemic 2VO animals displayed scattered ischemic infarcts and mild white matter injury. Conclusions. Short-term hyperglycemia affords robust protection against retinal hypoperfusion injury, but in the same animals, brain injury is not ameliorated. The mechanism of this retinal hyperglycemia-induced neuroprotection requires further study.
authors.affiliation: Ophthalmic Research Laboratories, South Australian Institute of Ophthalmology, Hanson Institute Centre for Neurological Diseases, Adelaide, South Australia, Australia.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Holman
authors.forename: Glyn
authors.initials: G
authors.lastname: Chidlow
authors.forename: John P M
authors.initials: JP
authors.lastname: Wood
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Casson
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002545:Brain Ischemia / Q000503:physiopathology*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006943:Hyperglycemia / Q000378:metabolism / Q000503:physiopathology*; D007124:Immunoenzyme Techniques; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D064231:Nestin; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology*; D012164:Retinal Diseases / Q000503:physiopathology*; D055351:Retinal Neurons / Q000378:metabolism / Q000473:pathology; D012171:Retinal Vessels / Q000503:physiopathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C100745:Aif1 protein, rat; D001786:Blood Glucose; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D055551:HSP27 Heat-Shock Proteins; C486114:Hspb1 protein, rat; D007381:Intermediate Filament Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D012333:RNA, Messenger