Expression of ATP-binding cassette transporters at the inner blood-retinal barrier in a neonatal mouse model of oxygen-induced retinopathy.
ATP-binding cassette (ABC) transporters at the blood-brain barrier (BBB) are responsible for the majority of the transcellular movement of various substrates, including various drugs, and contribute to the maintenance of brain homeostasis. Clinically, the abnormal expression of efflux transporters at the BBB is known to be associated with brain diseases such as epilepsy. In the retina, vascular endothelial cells outline the inner blood-retinal barrier (BRB) like the BBB, and some ABC efflux transporters are expressed in the adult retina. However, little is known about ABC transporter expression during retinal development or under pathological conditions. Here, we examined ABC transporter expression in the mouse retina, and demonstrated that P-glycoprotein (P-gp)/ABCB1, Mrp4/ABCC4, and Bcrp/ABCG2 were almost uniformly expressed in these blood vessels, including the capillaries and large vessels. This expression persisted throughout the developmental period, and the hyaloid vessels that normally feed the developing eye were immunoreactive for P-gp and Mrp4. Furthermore, we investigated ABC transporter expression in pathological angiogenesis using an oxygen-induced retinopathy model where hypoxia-induced preretinal neovascularization occurred around the central avascular retina. P-gp was prominently immunoexpressed but Mrp4 and Bcrp were weakly immunoexpressed, in the preretinal neovascular tufts. These findings will be helpful for understanding the roles of ABC transporters during both physiological and pathological retinal angiogenesis, and might provide new insights for safe and effective drug administration to infants or patients with angiogenic ocular disease.
Tagami
Mizuki
M
Department of Surgery, Division of Ophthalmology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
Kusuhara
Sentaro
S
Honda
Shigeru
S
Tsukahara
Yasutomo
Y
Negi
Akira
A
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008833:Microcirculation / Q000502:physiology; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D010100:Oxygen / Q000009:adverse effects*; D012160:Retina / Q000254:growth & development / Q000378:metabolism* / Q000503:physiopathology; D012161:Retinal Artery / Q000254:growth & development / Q000378:metabolism* / Q000503:physiopathology; D012178:Retinopathy of Prematurity / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010100:Oxygen; C489540:Abcc4 protein, mouse; C501412:Abcg2 protein, mouse