Suppressed expression of tubedown-1 in retinal neovascularization of proliferative diabetic retinopathy

Purpose. Retinal neovascularization occurring as a complication of diabetes mellitus can cause vision loss and blindness. The identification and study of novel genes involved in retinal angiogenesis may define new targets to suppress retinal neovascularization in diabetes and other ocular diseases. A novel acetyltransferase subunit, tubedown-1 (tbdn-1), has been isolated, the expression of which is regulated during blood vessel development. Tbdn- 1 is not detected in most adult vascular beds but persists at high levels i n the adult ocular vasculature. The purpose of this study was to gain insig ht into the possible role of tbdn-1 in retinal blood vessels by characteriz ing its expression patterns in adult homeostasis and in retinal neovascular ization associated with diabetes. Methods. Western blot analysis and immunohistochemistry were performed to s tudy the expression patterns of tbdn-1 during adult homeostasis in normal h uman retinas, in a model of choroid-retina endothelial capillary outgrowth in vitro, and in retinas showing neovascularization in patients with prolif erative diabetic retinopathy (PDR). Results. In adults during homeostasis. tbdn-1 was expressed highly in norma l endothelium of retinal and limbic blood vessels. Tbdn-1 was also expresse d in RF/6A, a rhesus macaque choroid-retina-derived endothelial cell line. In an in vitro model system using the RF/6A cell line, tbdn-1 expression wa s downregulated during the outgrowth of these cells into capillary-like str uctures on a reconstituted basement membrane matrix. Similar to this in vit ro model, tbdn-1 expression is specifically suppressed in the endothelial c ells of blood vessels and capillary fronds in vivo in both the neural retin al tissue and in preretinal membranes in eyes of patients with PDR. Conclusions. High levels of expression of tbdn-1 are associated with ocular endothelial homeostasis in adults. Conversely, low levels of tbdn-1 expres sion are associated with endothelial capillary outgrowth in vitro and retin al neovascularization in vivo. Because the tbdn-1 acetyltransferase subunit is a member of a family of regulatory enzymes that are known to control a range of processes, including cell growth and differentiation, through post translational modification. the current results support a hypothesis that t bdn-1 may be involved in maintaining homeostasis and preventing retinal neo vascularization.