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Marina Renner, Stephanie Lohmann, Dustin Schulte, Gesa Stute, H Burkhard Dick, Stephanie C. Joachim; Ranibizumab and Bevacizumab treatment after retinal ischemia-reperfusion injury in a rodent model. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3325.
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© ARVO (1962-2015); The Authors (2016-present)
Ischemia-reperfusion (I/R) results in functional and morphological damage of different retinal cell types. The aim of this study was to investigate the effects of intravitreal ranibizumab and bevacizumab treatment, VEGF inhibitors, on retinal cells after ischemic injury.
I/R was induced by raising the IOP to 140 mmHg for 1h in one eye of rats (n=5-6/group). One day after I/R the VEGF inhibitors were intravitreally injected. The untreated eye served as control (Co). 14 days after ischemia ERG measurements were performed. Retinal ganglion cells (Brn-3a), microglia (Iba1) as well as activated microglia (ED1) were stained on retinal cross-sections. Additionally, apoptosis (Bax) and the early (LC3BII) and late (LAMP1) autophagocytosis were analyzed using immunohistochemistry. Labeled cells were counted followed by group comparisons (ANOVA with tukey post-hoc test).
Significant reduction of a- (p<0.05) and b-wave (p=0.0001) amplitudes was noted in ERGs of all ischemic groups. The amplitudes of the bevacizumab group were comparable to the I/R group, whereas increase could be observed on amplitudes of the a- and b-wave of the ranibizumab group in comparison to I/R. Significantly fewer Brn-3a+ cells were evaluated in ischemic (p<0.001) and bevacizumab treated (p=0.019) retinas, not in ranibizumab ones compared to control. A significantly higher rate of apoptotic cells was revealed only in the I/R group (p=0.005), but not in treated groups. Ischemic and bevacizumab treated eyes displayed significantly more autophagozytotic cells (p=0.009) than the ranibizumab group. Furthermore, a significant microglial immigration and activation was detected in all ischemic groups (p<0.05) compared to control. However, a decrease of Iba1+ and ED1+ cells could be observed in ranibizumab treated retinas.
Our data suggest that VEGF inhibitors have a protective effect on functionality and appearance of retinal ganglion cells after ischemic injury. In our study the efficiency of ranibizumab was greater than that of the off-label used bevacizumab. We suppose that the different effectiveness is due to the higher binding affinity and the smaller molecule size of ranibizumab which allows better retinal penetration. Thus, VEGF inhibitors represent an option to treat retinal ischemic damage.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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