TY - JOUR
T1 - Studies on the mechanism of vessel regression in a rat model of ROP
AU - Hemo, I.
AU - Pe'er, J.
AU - Alon, T.
AU - Itin, A.
AU - Stone, J.
AU - Keshet, E.
PY - 1996/2/15
Y1 - 1996/2/15
N2 - Purpose. The initiating event in ROP pathogenesis is obliteration of newly-formed vessels as a consequence of exposure to hyperoxia. The purpose of this study was to gain further insights into the mechanism of hyperoxia-induced vessel regression. Methods. Newborn rats were exposed to hyperoxia at postnatal day 7, with or without prior intraocular injection of VEGF. Two days later, whole-mount retina preparations were examined for the integrity of the vascular network (by lectin immunohistochemistry), for apoptotic cells (by TUNEL), and for VEGF expression (by in situ hybridization). Results. Consistent with the thesis that hyperoxia-induced vessel regression represents an exaggeration of the natural process of vascular 'pruning', vulnerability to excess oxygen was maximal at the time where the natural trimming of the vascular tree is taking place. Hyperoxia-induced regression is by an apoptotic mechanism and is preceded by down-regulation of endogenous VEGF expression by glial cells (astrocytes and Muller cells). Intraocular injection of VEGF just prior to the hyperoxic insult prevented vessel regression. When inspected following 5 days at room air, VEGF-injected eyes showed less vascular damage (e.g. less intraretinal hemorrhage and improved vascular patency) than mock-injected eyes. Conclusions. VEGF may act as a survival factor for newly-formed retinal vessels, and its down-regulation by hyperoxia might be an important factor in ROP-associated obliteration of immature vessels.
AB - Purpose. The initiating event in ROP pathogenesis is obliteration of newly-formed vessels as a consequence of exposure to hyperoxia. The purpose of this study was to gain further insights into the mechanism of hyperoxia-induced vessel regression. Methods. Newborn rats were exposed to hyperoxia at postnatal day 7, with or without prior intraocular injection of VEGF. Two days later, whole-mount retina preparations were examined for the integrity of the vascular network (by lectin immunohistochemistry), for apoptotic cells (by TUNEL), and for VEGF expression (by in situ hybridization). Results. Consistent with the thesis that hyperoxia-induced vessel regression represents an exaggeration of the natural process of vascular 'pruning', vulnerability to excess oxygen was maximal at the time where the natural trimming of the vascular tree is taking place. Hyperoxia-induced regression is by an apoptotic mechanism and is preceded by down-regulation of endogenous VEGF expression by glial cells (astrocytes and Muller cells). Intraocular injection of VEGF just prior to the hyperoxic insult prevented vessel regression. When inspected following 5 days at room air, VEGF-injected eyes showed less vascular damage (e.g. less intraretinal hemorrhage and improved vascular patency) than mock-injected eyes. Conclusions. VEGF may act as a survival factor for newly-formed retinal vessels, and its down-regulation by hyperoxia might be an important factor in ROP-associated obliteration of immature vessels.
UR - http://www.scopus.com/inward/record.url?scp=33750170723&partnerID=8YFLogxK
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AN - SCOPUS:33750170723
SN - 0146-0404
VL - 37
SP - S132
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
IS - 3
ER -