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J.-W. Jang, H. Lim, K.-S. Kim, K.-C. Ko, O.-W. Kwon, D.-S. Kim; Preclinical Evaluation of EG-Mirotin and Comparison With Anti-VEGF Agents for Ischemic Retinal Diseases. Invest. Ophthalmol. Vis. Sci. 2008;49(13):884.
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It has been previously reported that EG-Mirotin, a recombinant human RGD motif containing-polypeptide, is a novel therapeutic polypeptide for ischemic retinal diseases. In this study, the preclinical assessment of this therapeutic candidate and comparison with commercialized anti-VEGF agent, Abciximab and Bevacizumab, against ischemic retinal disorders were investigated.
To determine the therapeutic ranges and optimal administration route, mouse ROP model which is characterized by vascular leakage, ischemia and abnormal ocular neovascularization was used. The safety of systemic administration of EG-Mirotin to cancer patients was verified by the murine bladder tumor cell-line (MBT-2) transplantation mouse model. And the therapeutic potent of EG-Mirotin for ischemic retinal disorders was additionally compared with Abciximab and Bevacizumab, in relative thickness of ganglion cell layer, blood vessel profiles (BVPs) and retinopathy score as evaluation criteria.
The effective normalization of retinal superficial layer of EG-Mirotin was observed in a dose range between 5 µg/ kg and 10 µg/ kg. In the administration route study, there is no significant difference between intraperitoneal (i.p.) and intramuscular (i.m.) injection. Additionally, the side effects which would be accelerated tumor growth by systemic administration of EG-Mirotin were not observed. Hypo-perfused area was about 30% of retinal field in ROP control, similarly the results were also observed in Abciximab and Bevacizumab treated groups. However, EG-Mirotin induced blood vessels maturation and improvement of abnormality unlike the anti-VEGF agents that only inhibit angiogenesis. It also decreased not only the edema of retina but also the pathological and histological lesions such as vascular tuft and blood vessels profile.
In conclusion, the proper clinical route and dose of EG-Mirotin for ischemic retinal diseases are i.m administration with 10 µg/ kg. This drug is as safe as to be able to systemically administration into cancer patients in the clinical use. This study also demonstrates that EG-Mirotin has a strong therapeutic potential which induces the normalization of impaired vessels and the maturation of them in the ischemic retina at early stage of diseases, contrary to anti-VEGF agents that inhibit only angiogenesis at late stage.
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