Transient ischemic injury in the rat retina caused by thrombotic occlusion-thrombolytic reperfusion.
OBJECTIVE
To establish a clinically relevant model of transient retinal ischemia by thrombotic occlusion-thrombolytic reperfusion of the central retinal artery of the rat.


METHODS
Thrombus was photochemically induced in the central retinal artery by the combination of intravenous injection of photo-sensitive dye, rose bengal, and green laser irradiation focused on the artery. Transient retinal ischemia for 60 minutes was achieved by a subsequent systemic administration of tissue-type plasminogen activator to reperfuse the occluded vessel. Samples of retinas were excised from the animals killed 3, 9, 12, 24, 48, and 78 hours after the reperfusion. The experimental data were processed using the TdT-dUTP terminal nick-end labeling (TUNEL) method to detect apoptotic cells.


RESULTS
The transient retinal ischemia caused time-sequential apoptotic changes in the retinal cells as evaluated by counting the number of TUNEL-positive cells. The most remarkable changes occurred in the central area of retina, and further on the sections taken 24 hours after reperfusion. The peripheral area was less affected, and the outer nuclear cell layer was almost unaffected throughout the observation period.


CONCLUSIONS
The proposed method to cause retinal transient ischemia is highly reproducible, and it is easy to simulate the progress and topographical distribution of retinal changes observed in the clinical cases of central retinal arterial occlusion and its subsequent thrombolytic reperfusion. This may provide a useful tool for constructing the effective thrombolytic strategies against the central retinal arterial occlusion and for evaluating the effects of neuroprotective agents.
Department of Pharmacology, Gifu University School of Medicine, Japan. lina-gif@umin.u-tokyo.ac.jp
L
L
Daugeliene
M
M
Niwa
A
A
Hara
H
H
Matsuno
T
T
Yamamoto
Y
Y
Kitazawa
T
T
Uematsu
D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D005343:Fibrinolytic Agents / Q000008:administration & dosage; D005456:Fluorescent Dyes / Q000008:administration & dosage; D020287:In Situ Nick-End Labeling; D007834:Lasers; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000209:etiology* / Q000473:pathology; D015356:Retinal Artery Occlusion / Q000139:chemically induced / Q000150:complications* / Q000473:pathology / Q000628:therapy; D012164:Retinal Diseases / Q000209:etiology* / Q000473:pathology; D012171:Retinal Vessels / Q000187:drug effects / Q000473:pathology* / Q000528:radiation effects; D012395:Rose Bengal / Q000008:administration & dosage; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage
D005343:Fibrinolytic Agents; D005456:Fluorescent Dyes; D012395:Rose Bengal; D010959:Tissue Plasminogen Activator