Structural consequences after intravitreal bevacizumab injection without increasing apoptotic cell death in a retinopathy of prematurity mouse model

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ABSTRACT.Purpose:To evaluate the effect of different bevacizumab concentrations on retinal endothelial cell proliferation, retinal structures and apoptotic activity after intravitreal injection in a retinopathy of prematurity (ROP) mouse model.Methods:A total of 35 of C57BL/J6 mice were exposed to 75 ± 2% oxygen from postnatal day 7 to postnatal day 12. On day 12, 10 mice (group C) were injected with 2.5 μg intravitreal bevacizumab (IVB), 11 mice (group D) were injected with 1.25 μg IVB, and 14 mice (group E) were injected with 0.625 μg IVB in one eye. The contralateral eyes were injected with isotonic saline (control group = group B). Four nonexposed mice served as negative controls (group A). Neovascularization was quantified by counting the endothelial cell proliferation on the vitreal side of the inner limiting membrane of the retina. Histological and ultrastructural changes were examined by light and electron microscopy. Terminal deoxynucleotidyl transferase deoxy-UTP-nick end labelling (TUNEL) was used to detect apoptosis.Results:The endothelial cell count per histological section was lower in groups C (p < 0.0001), D (p < 0.0001) and E (p < 0.0001) compared with the control group B. Histological evaluation showed no retinal toxicity in any group. Electron microscopy revealed hyperoxia-induced mitochondrial dysmorphology in group B. Mitochondrial dysmorphology displayed dose-dependent gradual increase in IVB-injected eyes. Intravitreal bevacizumab induced no significant increase in apoptotic cell death.Conclusion:Bevacizumab suppresses endothelial cell proliferation in a ROP mouse model. In addition to hyperoxia-induced mitochondrial dysmorphology of C57BL/J6 retina, morphological findings implicate further mitochondrial vulnerability because of bevacizumab without increase in apoptotic cell death.

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