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Michelle R. Smith, Robinette King, Brian J. Raisler; Endorepellin: Antiangiogenic Effects In The Oxygen Induced Retinopathy Model. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1370.
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To determine the efficacy of endorepellin, a C-terminal peptide derivative of perlecan, in the oxygen induced retinopathy mouse model.
Endorepellin was administered by intravitreal injection entering at the ora serrata in neonatal mice. Contralateral eyes were injected with vehicle. We used three dose levels (0.01 ug, 0.1 ug, or 1 ug) and time points at post-natal days 7 (P7), P12, P14, or P16. Varying dosages determine a dose response curve. Treatment at different time points during the model reflect preventative versus palliative measures. Neovascular response was assessed by H&E stained paraffin embedded cross-sections to enumerate endothelial nuclei internal to the ILM. We performed IHC of serial sections for endothelial markers CD31and Ki67, and for alpha2beta1 integrin. Additionally, FITC-dextran perfused retinal flat-mounts were analyzed to determine hyperfluorescence due to neovascular tufts and to semi-quantitatively assess anti-angiogenic effects.
Administration of endorepellin immediately after return to room air (P12) was effective in controlling NV. In eyes treated with endorepellin, nuclei internal to the ILM numbered significantly lower than control eyes (6.15 nuclei per section versus 29.24, n=6). IHC analysis showed positive staining for CD31 and Ki67, indicating the presence of proliferating endothelial cells was reduced in endorepellin treated eyes while extant vessels were unaffected. Staining for alpha2beta1 integrin revealed the interaction of endorepellin with endothelial cells through this receptor for collagen-1. FITC-dextran perfused retinal flat mounts showed a decreased hyperfluorescence due to leaking neovascular tufts in eyes treated with endorepellin versus those treated with vehicle.
Endorepellin has previously been demonstrated to be an effective anti-angiogenic; limiting tumor growth by supressing neovascularization. Here we conclude that treatment with endorepellin reduces neovascularization in the oxygen induced retinopathy model in C57 mice. While the use of endorepellin is still far from clinical application, the reduction NV seen in endorepellin treated eyes shows promise for eventual clinical use of endorepellin as a possible therapy for retinopathy of prematurity.
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