Effect of octreotide acetate on endothelial cell proliferation and retinal morphology in an in vivo mouse model of retinopathy of prematurity

The aim of the study was to investigate the effects of Octreotide acetat, at different concentrations, on retinal endothelial cell proliferation and retinal morphological structure in an oxygen-induced retinopathy of preamturity (ROP) mouse model. In vivo analysis were performed using ROP mouse model with C57BL7J6 newborn mouse. There were four groups (group-1=negative control group), group-2=control group, group-3=0.1μg IVO enjected group, group-4= 0.05μg IVO). Twentysix C57BLJ6 mice were exposed to 75% oxygen from postnatal day 7(P7) to 12 (P12). On day 12 Octreotide acetat 0.1μg was administered intravitreally to one eye of 12 mice (group 3), 0.05μg Octreotide acetat to one eye of 14 mice (group 4) and contralateral eyes (group-2 n=26) received isotonic saline. Four mice of the same age that had been kept in room air without any exposition to high oxygen were used as negative kontrol. On day 17, the mice were sacrificed and eyes enucleated for quantitative analysis of preretinal neovascularisation. Neovascularizations were quantified by counting the endothelial cell nuclei on the vitreal side of the inner limiting membrane of the retina. Histological and ultrastructural changes were examined by using light and electron microscopy. The endothelial cell count, per histological section in the control group was significanly higher compared with group 3 ( p<0.0001) and group 4 (p=0.01). In grup-1 (negative kontrol group) there were no endothelial cell nuclei detected on the vitreal side of the inner limitig membrane. Histologic evaluation of retinal layers using light microscopy showed no retinal toxicity in any group. Electron microscopy revealed similar mitochondrial dysmorphology in group-2 and grup-4, but mitochondrial dysmorphology displayed increase in group- 3. In conclusion we can say that intravitreal injection of octreotide acetat supresses endothelial cell proliferation in a ROP mouse model. In addition to hyperoxia induced vulnerability of C57BL/J6 retina, morphological findings implicate further ultrastructural vulnerability due to octreatid acetate.