TRAIL-deficient mice exhibit delayed regression of retinal neovascularization

Kristin E. Hubert, Michael H. Davies, Andrew J. Stempel, Thomas S. Griffith, Michael R. Powers

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

While it is well established that tumor necrosis factorrelated apoptosis-inducing ligand (TRAIL) induces apoptosis in various cell types, the role of TRAIL in regulation of retinal neovascularization (NV) has not been described. Here we determined the role of TRAIL in retinal NV during oxygen-induced retinopathy using TRAIL deficient (-/-) mice. TRAIL and its receptor, DR5, were expressed in wild-type retinas at all time points evaluated (postnatal days 12, 17, 21, 24) during oxygen-induced retinopathy and in agematched room air control animals. Localization of TRAIL+ cells within the neovascular tufts of hyperoxiaexposed wild-type mice suggested TRAIL plays a role in oxygen-induced retinopathy. Retinal vascular development appeared normal in the TRAIL-/- mice, except for a small but significant difference in the capillary-free zone surrounding major arteries. A minimal difference in avascularity was observed at postnatal day 12 in the retinas of TRAIL-/- mice after hyperoxia-exposure compared with wild-type mice, suggesting that TRAIL does not play a major role in the vaso-obliterative phase of oxygen-induced retinopathy. However, at the peak of NV, TRAIL-/- mice had a significant increase in retinal neovascularization. In addition, when NV naturally regresses in wild-type mice, TRAIL-/- mice continued to display significantly high levels of NV. This was attributed to a significant decrease in neovascular tuft cells undergoing apoptosis in TRAIL-/- mice. Together, these data strongly suggest that TRAIL plays a role in the control of retinal NV.

Original languageEnglish (US)
Pages (from-to)2697-2708
Number of pages12
JournalAmerican Journal of Pathology
Volume175
Issue number6
DOIs
StatePublished - 2009

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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