Intravitreal anti-VEGF therapy blocks inflammatory cell infiltration and re-entry into the circulation in retinal angiogenesis.
OBJECTIVE
Anti-VEGF-A antibody (Ab) (e.g., bevacizumab, ranibizumab) is widely used as a treatment against retinal angiogenesis and edema. The purpose of this study was to evaluate whether intravitreal anti-VEGF Ab injection modulates inflammatory cells in retinal angiogenesis.


METHODS
To investigate whether intravitreal bevacizumab injections affect the number of inflammatory cells in proliferative diabetic retinopathy (PDR) membranes in patients, immunohistochemical staining with CD45 Ab (pan-leukocyte marker) was performed using the surgically obtained membranes in pars plana vitrectomy with or without pretreatment with bevacizumab. To check whether anti-VEGF-A Ab affects leukocytes going in and out of blood vessels during retinal angiogenesis, the authors performed their novel leukocyte transmigration assay and CD45 immunostaining in a mouse model of oxygen-induced retinopathy (OIR).


RESULTS
The authors' new imaging approach revealed that intravitreal injection of anti-VEGF-A Ab blocks leukocyte infiltration as well as angiogenesis. The Ab injection inhibited leukocyte transmigration before affecting the angiogenenic area. CD45 staining showed no significant difference in the leukocyte number in the angiogenic retina or the human PDR membranes between the anti-VEGF-A Ab injected group and the control group. Furthermore, VEGF-A inhibition also affected leukocytes going out from the retina.


CONCLUSIONS
Intravitreal injection of anti-VEGF-A Ab could inhibit leukocyte trafficking in the retina, suggesting that anti-VEGF-A therapy could serve as a treatment in retinal inflammation.
Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, and Fucuoka University Chikushi Hospital, Fukuoka, Japan. snakao@med.kyushu-u.ac.jp
Shintaro
S
Nakao
Mitsuru
M
Arima
Keijiro
K
Ishikawa
Riichiro
R
Kohno
Shuhei
S
Kawahara
Masanori
M
Miyazaki
Shigeo
S
Yoshida
Hiroshi
H
Enaida
Ali
A
Hafezi-Moghadam
Toshihiro
T
Kono
Tatsuro
T
Ishibashi
D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D000831:Animals, Newborn; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000068258:Bevacizumab; D002465:Cell Movement / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D058449:Intravitreal Injections; D008268:Macular Degeneration / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D000069579:Ranibizumab; D012160:Retina / Q000378:metabolism; D015861:Retinal Neovascularization / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D000069579:Ranibizumab