The effect of hyperglycemia on experimental retinal ischemia.
OBJECTIVE
To determine the effect of hyperglycemia and intraocular glucose delivery on ischemic retinal injury.


METHODS
Experimental diabetes was induced in age- and sex-matched Wistar rats by an injection of streptozocin. The functional and structural retinal injury in these rats after a period of pressure-induced retinal ischemia was compared with the injury in appropriate controls and with rats made hyperglycemic by an injection of systemic glucose. The effect of high intraocular pressure-induced ischemia with the use of several different isotonic substrates in the elevated reservoir (isotonic sodium chloride solution, glucose, 2-deoxyglucose, and lactate) was also determined. Electroretinography, reverse transcriptase polymerase chain reaction, and histologic examination were used to assess the retinal injury.


RESULTS
Streptozocin-induced diabetes, glucose injection-induced preexisting hyperglycemia, and intraocular glucose delivery during ischemia markedly reduced the functional and structural ischemic retinal injury. Neither postischemic hyperglycemia nor the intraocular delivery of lactate significantly affected the ischemic injury; however, the intraocular delivery of 2-deoxyglucose significantly exacerbated the retinal injury.


CONCLUSIONS
Preexisting hyperglycemia and the intraocular delivery of glucose markedly attenuate ischemic retinal injury. Clinical Relevance These findings highlight fundamental differences in energy metabolism between brain and retina, have important implications for the pathophysiology of diabetic retinopathy, and may lead to novel therapeutic strategies for ischemic retinopathies.
Nuffield Laboratory of Ophthalmology, Oxford University, Oxford, England.
Robert J
RJ
Casson
Glyn
G
Chidlow
James P M
JP
Wood
Neville N
NN
Osborne
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D021983:Cyclophilins / Q000235:genetics; D003847:Deoxyglucose / Q000008:administration & dosage; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D004596:Electroretinography; D005947:Glucose / Q000008:administration & dosage; D006943:Hyperglycemia / Q000378:metabolism / Q000503:physiopathology*; D007552:Isotonic Solutions / Q000008:administration & dosage; D019344:Lactic Acid / Q000008:administration & dosage; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology*; D012160:Retina / Q000378:metabolism; D012164:Retinal Diseases / Q000378:metabolism / Q000503:physiopathology*; D012171:Retinal Vessels / Q000503:physiopathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018800:Thy-1 Antigens / Q000235:genetics; D014822:Vitreous Body / Q000378:metabolism
D001786:Blood Glucose; D007552:Isotonic Solutions; D012333:RNA, Messenger; D018800:Thy-1 Antigens; D019344:Lactic Acid; D003847:Deoxyglucose; D021983:Cyclophilins; D005947:Glucose