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 language | English (US) |
|---|---|
| Pages (from-to) | 2697-2708 |
| Number of pages | 12 |
| Journal | American Journal of Pathology |
| Volume | 175 |
| Issue number | 6 |
| DOIs | |
| State | Published - 2009 |
Bibliographical note
Funding Information:Supported by grants NEI EY011548 (to M.R.P.), NEI EY10572 (core grant), NCI CA109446 (to T.S.G.), and the N.L. Tartar Research Fund (K.E.H.), and an unrestricted grant from Research to Prevent Blindness. This publication was made possible with support from the Oregon Clinical and Translational Research Institute, grant number UL1 RR024140 from the National Center for Research Resources, a component of the NIH, and the NIH Roadmap for Medical Research.