Tubedown-1 (Tbdn-1) suppression in oxygen-induced retinopathy andin retinopathy of prematurity

[摘要] Purpose: Identification of unique proteins involved in retinopathyof prematurity (ROP) may facilitate new and more effective diagnostictools and molecular-based treatments for ROP. Tubedown-1 (Tbdn-1), anovel homeostatic protein which copurifies with an acetyltransferaseactivity, is expressed in normal retinal endothelium and is specificallysuppressed in retinal endothelial cells from patients with proliferativediabetic retinopathy. Furthermore, recent in vivo knockdown studies inmice have revealed that Tbdn-1 is important for retinal blood vesselhomeostasis and for preventing retinal neovascularization in adults. Thepurpose of the present study was to determine if the expression patternof Tbdn-1 is altered during oxygen-induced retinal neovascularization inmice and in a specimen of stage 3 human ROP.Methods: Specimens of oxygen-induced retinal neovascularization inmice, and a single specimen of active stage 3 ROP were studied byimmunohistochemistry and digital image analysis using antibodies raisedagainst Tbdn-1 and other blood vessel markers.Results: The pattern of Tbdn-1 expression during the course ofoxygen-induced retinal neovascularization in mice suggests a regulatingrole in neonatal retinopathy. Retinal lesions from oxygen-inducedretinal neovascularization in mice display suppression of retinalendothelial Tbdn-1 protein expression in conjunction with an increase inexpression of proliferating cell nuclear antigen (a marker ofproliferation) and α smooth muscle actin (a marker ofmyofibroblastic cells). Abnormal blood vessels within vitreoretinalneovascular lesions in a human specimen of active stage 3 ROP did notshow Tbdn-1 protein expression.Conclusions: These results suggest that the loss of retinalendothelial Tbdn-1 expression may be a contributing factor in retinalblood vessel proliferation in ROP.

[学科分类] 生物化学/生物物理