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Robert L. Gendron, William V. Good, Lisa C. Adams, Hélène Paradis; Suppressed Expression of Tubedown-1 in Retinal Neovascularization of Proliferative Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2001;42(12):3000-3007.
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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 in the adult
ocular vasculature. The purpose of this study was to gain insight into
the possible role of tbdn-1 in retinal blood vessels by characterizing
its expression patterns in adult homeostasis and in retinal
neovascularization associated with diabetes.
methods. Western blot analysis and immunohistochemistry were performed to study
the expression patterns of tbdn-1 during adult homeostasis in normal
human retinas, in a model of choroid–retina endothelial capillary
outgrowth in vitro, and in retinas showing neovascularization in
patients with proliferative diabetic retinopathy (PDR).
results. In adults during homeostasis, tbdn-1 was expressed highly in normal
endothelium of retinal and limbic blood vessels. Tbdn-1 was also
expressed 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 was downregulated during the outgrowth of these
cells into capillary-like structures on a reconstituted basement
membrane matrix. Similar to this in vitro model, tbdn-1 expression is
specifically suppressed in the endothelial cells of blood vessels and
capillary fronds in vivo in both the neural retinal 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
expression are associated with endothelial capillary outgrowth in vitro
and retinal 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 posttranslational modification, the
current results support a hypothesis that tbdn-1 may be involved in
maintaining homeostasis and preventing retinal
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