Abstract
Abstract: :
Purpose: Vascular endothelial growth factor (VEGF) is an angiogenic polypeptide that is expressed in response to hypoxic conditions. Recent in vitro experiments have suggested a direct neuroprotective effect of VEGF on certain neurons. The purpose of this study was to investigate the potential neuroprotective roles of specific VEGF isoforms in the neural retina in a model of ischemic preconditioning. Methods:Transient retinal ischemia was induced in male rats by temporary ligation of the optic nerve. To evaluate the protective effects of VEGF, ischemic preconditioning (5 minutes of ischemia) was induced 24 hours before a subsequent 60 minutes of ischemia. The expression of VEGF was determined by RT–PCR. Apoptotic cells in the retina were stained using the TdT–dUTP terminal nick–end labeling (TUNEL) assay and were counted 24 hours following reperfusion. To evaluate the neuroprotective effects of exogenous VEGF, either VEGF120 or VEGF164 was administrated intravitreally immediately following reperfusion. Results:RT–PCR showed increased expression of the VEGF120 and VEGF164 isoforms in retina following ischemic preconditioning. The number of apoptotic cells decreased in the preconditioned retinas. This protective effect was reversed by blocking all VEGF isoforms using a soluble receptor antagonist (sFlt–1–Fc), but not by blocking solely the VEGF164 isoform. Moreover, local administration of VEGF120 or VEGF164 displayed similar neuroprotective effects, in a dose dependent manner. Interestingly, post–ischemic retinas treated with VEGF164 demonstrated hemorrhaging, suggesting a potential increase in vascular leakage. Conclusions:These findings may have implications for the use of pan–VEGF isoform antagonists in the retina and highlight a possible role for VEGF120 as a therapeutic agent in ischemic diseases.
Keywords: growth factors/growth factor receptors • neuroprotection • ischemia