Effective and selective prevention of retinal leukostasis in streptozotocin-induced diabetic rats using gliclazide.
OBJECTIVE
Early stage leukocyte entrapment in the retinal microcirculation (retinal leukostasis) is considered to be one of the important pathogenetic events in diabetic retinopathy. Gliclazide, a sulphonylurea, was reported to reduce leukocyte adhesion to endothelial cells in hyperglycaemia in vitro, thus suggesting possible selective efficacy of this sulphonylurea in preventing leukostasis in diabetic patients. This study evaluated the effectiveness and selectivity of gliclazide treatment on retinal leukostasis of diabetic rats in vivo.


METHODS
Streptozotocin (STZ) (65 mg/kg)-induced diabetic rats were divided into three groups (n = 8 each): an untreated diabetic group, a gliclazide-treated diabetic group, and a glibenclamide-treated diabetic group. Gliclazide or glibenclamide was administered orally during a 3-week period. Non-diabetic rats were used as a control (n = 8). Retinal leukostasis was quantitatively evaluated in vivo by acridine orange leukocyte fluorography using a scanning laser ophthalmoscope.


RESULTS
The number of leukocytes trapped in the area around the optic disc in the untreated diabetic group (36.9 +/- 5.1 cells) increased significantly compared with the non-diabetic control group (21.9 +/- 2.9 cells; p = 0.0007). The number of leukocytes trapped in the gliclazide-treated diabetic group (23.5 +/- 4.0 cells) decreased significantly compared with untreated diabetic group ( p = 0.0008). In contrast, no reduction of retinal leukostasis was found in the glibenclamide-treated diabetic group (37.8 +/- 5.8 cells; p = 0.7923).


CONCLUSIONS
This suggests that gliclazide could directly improve abnormalities in the retinal microcirculation independent of blood glucose control and possibly have selective therapeutic benefits in preventing early, critical events in diabetic retinopathy compared with other sulphonylurea drugs.
Kinoshita
N
N
Department of Ophthalmology, Omiya Medical Center, Jichi Medical School, Saitama, Japan.
Kakehashi
A
A
Inoda
S
S
Itou
Y
Y
Kuroki
M
M
Yasu
T
T
Kawakami
M
M
Kanazawa
Y
Y
D000818:Animals; D002448:Cell Adhesion; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D003930:Diabetic Retinopathy / Q000517:prevention & control*; D005907:Gliclazide / Q000627:therapeutic use*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology; D018921:Leukostasis / Q000517:prevention & control*; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN
D007004:Hypoglycemic Agents; D005907:Gliclazide