IOVS Journal of Virology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

(Investigative Ophthalmology and Visual Science. 2004;45:3796-3805.)
© 2004 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.04-0052
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (14)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Brafman, A.
Right arrow Articles by Shoshani, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Brafman, A.
Right arrow Articles by Shoshani, T.

Inhibition of Oxygen-Induced Retinopathy in RTP801-Deficient Mice

Anat Brafman,1 Igor Mett,1 Millicent Shafir,1 Helen Gottlieb,1 Golda Damari,1 Sabrina Gozlan-Kelner,1 Vicktoria Vishnevskia-Dai,2 Rami Skaliter,1 Paz Einat,1 Alexander Faerman,1 Elena Feinstein,1 and Tzipora Shoshani1

1From Quark Biotech, Inc., Fremont, California; and the 2Department of Ophthalmology, Assaf Harofeh Medical Center, Sackler School of Medicine Tel-Aviv University, Zerifin, Israel.

PURPOSE. Ischemic proliferative retinopathy, which occurs as a complication of diabetes mellitus, prematurity, or retinal vein occlusion, is a major cause of blindness worldwide. In addition to retinal neovascularization, it involves retinal degeneration, of which apoptosis is the main cause. A prior report has described the cloning of a novel HIF-1–responsive gene, RTP801, which displays strong hypoxia-dependent upregulation in ischemic cells of neuronal origin, both in vitro and in vivo. Moreover, inducible overexpression of RTP801 promotes the apoptotic death of differentiated neuron-like PC12 cells and increases their sensitivity to ischemic injury and oxidative stress. The purpose of the study was to examine the potential role of RTP801 in the pathogenesis of retinopathy, using RTP801-deficient mice.

METHODS. Wild-type and RTP801-knockout mice were used in a model of retinopathy of prematurity (ROP). Their retinas were collected at postnatal day (P)14 and P17. They were examined by fluorescein angiography and by analysis of VEGF expression, neovascularization, and apoptosis.

RESULTS. The expression of RTP801 was induced in the wild-type retina after hypoxia treatment. The retinal expression of VEGF after transfer to normoxic conditions was similarly upregulated in both wild-type and knockout mice. Nevertheless, the retinas of the RTP801-knockout mice in an ROP model showed a significant reduction in retinal neovascularization (P < 0.0001) and in the number of apoptotic cells in the inner nuclear layer (P < 0.0001).

CONCLUSIONS. In the absence of RTP801 expression, development of retinopathy in the mouse model of ROP was significantly attenuated, thus implying an important role of RTP801 in the pathogenesis of ROP.




This article has been cited by other articles:


Home page
 J. Neurosci.Home page
C. Malagelada, Z. H. Jin, and L. A. Greene
RTP801 Is Induced in Parkinson's Disease and Mediates Neuron Death by Inhibiting Akt Phosphorylation/Activation
J. Neurosci., December 31, 2008; 28(53): 14363 - 14371.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. E. Sears, G. Hoppe, Q. Ebrahem, and B. Anand-Apte
Prolyl hydroxylase inhibition during hyperoxia prevents oxygen-induced retinopathy
PNAS, December 16, 2008; 105(50): 19898 - 19903.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
C. Malagelada, E. J. Ryu, S. C. Biswas, V. Jackson-Lewis, and L. A. Greene
RTP801 Is Elevated in Parkinson Brain Substantia Nigral Neurons and Mediates Death in Cellular Models of Parkinson's Disease by a Mechanism Involving Mammalian Target of Rapamycin Inactivation
J. Neurosci., September 27, 2006; 26(39): 9996 - 10005.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
A. L. Dorfman, O. Dembinska, S. Chemtob, and P. Lachapelle
Structural and functional consequences of trolox C treatment in the rat model of postnatal hyperoxia.
Invest. Ophthalmol. Vis. Sci., March 1, 2006; 47(3): 1101 - 1108.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
A. Sofer, K. Lei, C. M. Johannessen, and L. W. Ellisen
Regulation of mTOR and Cell Growth in Response to Energy Stress by REDD1
Mol. Cell. Biol., July 15, 2005; 25(14): 5834 - 5845.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2004 by the Association for Research in Vision and Ophthalmology