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Sentaro Kusuhara, Wataru Matsumiya, Makoto Nakamura; The role of Mrp4 in pathological angiogenesis of the mouse retina. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5894.
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© ARVO (1962-2015); The Authors (2016-present)
Mrp4 (multidrug resistance transporter 4) belongs to the ABC transporter family and protects healthy tissue by actively transporting xenobiotics and physiological substrates out of cells. We previously reported that Mrp4-/- mice exhibited suppressed retinal vascular development in response to forskolin treatment (Matsumiya W, et al. Invest Ophthalmol Vis Sci. 2012;53:8029-8035). Thus, this study aims to investigate the Mrp4 role in pathological retinal angiogenesis.
Oxygen-induced retinopathy (OIR) was produced by placing neonate mice in a 75% O2 chamber from P7 to P12 and keeping them at room air from P12 to P17. The eye balls were harvested at P17 and retinal whole-mount immunohistochemistry for CD31 was performed. The percentage of avascular area over total retinal area was calculated and the features of OIR were scored using Retinopathy Scoring System which consists of six parameters: blood vessel growth, blood vessel tufts, extra retinal neovascularization, central vasoconstriction, retinal haemorrhage, and blood vessel tortuosity (Higgins RD, et al. Curr Eye Res. 1999;18:20-27). Comparisons of the avascular area and Retinopathy scores were carried out between wild type (WT) mice and Mrp4-/- mice (n=4).
Mrp4-/- mice had a larger avascular area than WT mice (WT, 17.9±2.1%; Mrp4-/-, 29.1±4.0%; P=0.021). Mrp4-/- mice also obtained a higher Retinopathy score in two parameters (blood vessel tufts [WT, 2.3±0.5; Mrp4-/-, 3.8±0.5; P=0.028] and central vasoconstriction [WT, 1.3±0.5; Mrp4-/-, 3.0±0.0; P=0.017]) and in the total score as compared to WT mice (WT, 8.3±1.3; Mrp4-/-, 14.5±1.0; P=0.020).
Mrp4 may have suppressive effects on pathological retinal angiogenesis as Mrp4-/- mice showed more severe OIR phenotypes than WT mice.
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