Neuroprotective effects of D-allose against retinal ischemia-reperfusion injury.
OBJECTIVE
To investigate the effect of D-allose, a rare sugar, against ischemia reperfusion injury in the rat retina.


METHODS
Retinal ischemia was induced by increasing intraocular pressure to 130 mm Hg and maintaining that level for 45 minutes. Morphometric studies were performed to study the effect of D-allose on the histologic changes induced by ischemia in the rat retina. Glutamate release from the rat retina and intravitreal P(O2) profiles were monitored during and after ischemia with a microdialysis biosensor and oxygen-sensitive microelectrodes. The release of hydrogen peroxide stained with diaminobenzidine hydrochloride was monitored by an in vitro retinal ischemia model.


RESULTS
Seven days after the ischemia, significant reductions in both the number of ganglion cells and the thickness of the inner plexiform layer were observed. Pretreatment with D-allose significantly inhibited the ischemic injury of the inner retina. A large release of glutamate occurred during the ischemia. After the recirculation, glutamate levels were increased again and reached a maximum in approximately 20 minutes. The increases in extracellular glutamate during and after ischemia tend to be suppressed by administration of d-allose. d-Allose attenuated the increase in intravitreal P(O2) during reperfusion. After the ischemia, production of hydrogen peroxide was detected within approximately 30 minutes. D-allose suppressed the production of hydrogen peroxide.


CONCLUSIONS
These results suggest that D-allose may protect neurons by decreasing extracellular glutamate and attenuating oxidative stress in ischemic insult.
Department of Ophthalmology, Kagawa University Faculty of Medicine, Ikenobe, Miki, Japan. kazuyk@med.kagawa-u.ac.jp
Kazuyuki
K
Hirooka
Osamu
O
Miyamoto
Pan
P
Jinming
Yinghua
Y
Du
Toshifumi
T
Itano
Tetsuya
T
Baba
Masaaki
M
Tokuda
Fumio
F
Shiraga
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005947:Glucose / Q000627:therapeutic use*; D018698:Glutamic Acid / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D007429:Intraocular Pressure; D017736:Ion-Selective Electrodes; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010101:Oxygen Consumption; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D012164:Retinal Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D018696:Neuroprotective Agents; D018698:Glutamic Acid; C002055:allose; D006861:Hydrogen Peroxide; D005947:Glucose