Intravitreal injection of corticosteroid attenuates leukostasis and vascular leakage in experimental diabetic retina.
OBJECTIVE
Recently, intravitreal injection of corticosteroids has been in wide use as a treatment for diabetic macular edema, and the outcomes have been favorable. However, the exact mechanism remains unclear. The hypothesis for the current study was that intravitreal corticosteroids may improve diabetic retinal edema by amelioration of blood-retinal barrier (BRB) breakdown, by inhibiting leukocyte stasis (leukostasis).


METHODS
Diabetes was induced in 6-week-old male Long-Evans rats by intraperitoneal injection of streptozotocin (75 mg/kg). Three weeks after induction of diabetes, intravitreal injection of dexamethasone (40 microg/10 microL) was performed. At 2 days after intravitreal injection, accumulated leukocytes were counted in vivo by acridine orange leukocyte fluorography, and BRB breakdown was evaluated by measurement of retinal vascular permeability. The mRNA expression and protein levels of intercellular adhesion molecule (ICAM)-1 in the retina were also studied.


RESULTS
The number of leukocytes accumulated in the retina, once increased in the diabetic group, was decreased by 31.6% (P = 0.0001) after dexamethasone injection. The level of BRB breakdown, also elevated in the diabetic group, was suppressed by 61.1% (P = 0.0046) after dexamethasone injection. The level of ICAM-1 mRNA expression and its protein, upregulated in the diabetic group, were downregulated by dexamethasone treatment by 70.0% (P < 0.0001) and 56.4% (P = 0.0003).


CONCLUSIONS
Intravitreal injection of corticosteroids improves diabetic retinal edema through inhibiting leukocyte recruitment in the diabetic retina.
Tamura
Hiroshi
H
Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Miyamoto
Kazuaki
K
Kiryu
Junichi
J
Miyahara
Shinsuke
S
Katsuta
Hideto
H
Hirose
Fumitaka
F
Musashi
Kunihiro
K
Yoshimura
Nagahisa
N
D000165:Acridine Orange; D000818:Animals; D001813:Blood-Retinal Barrier / Q000187:drug effects*; D002199:Capillary Permeability / Q000187:drug effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005456:Fluorescent Dyes; D015590:Fluorophotometry; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use*; D007267:Injections; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D007962:Leukocytes / Q000502:physiology; D018921:Leukostasis / Q000517:prevention & control*; D008269:Macular Edema / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014822:Vitreous Body
D005456:Fluorescent Dyes; D005938:Glucocorticoids; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D003907:Dexamethasone; D000165:Acridine Orange