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Type I pig collagen enhances the efficacy of PEDF 34-mer peptide in a mouse model of laser-induced choroidal neovascularization

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Abstract

Background

Pigment epithelium-derived factor (PEDF)–derived 34-mer peptide (PEDF34, Asp44-Asn77) has anti-angiogenic activity but has limitations in clinical application because of an inverted bell–shaped dose-effect relationship and a short half-life. In this study, we attempted to mitigate these problems by mixing PEDF34 with type I collagen.

Methods

The anti-angiogenic activity of the PEDF34/atelocollagen mixture was evaluated by HUVEC tube formation assay and in a laser-induced choroidal neovascular (CNV) mouse model. PEDF34 and/or collagen were administrated using intravitreal injections or eye drops. CNV lesion size was quantified using FITC-dextran-perfused retinal whole mounts. Western blot analysis and inhibitor assays were used to define the action mechanisms of PEDF34 and the mixture.

Results

Collagen broadened the effective dose range of PEDF34 in the tube formation assay by > 250 times (from 0.2 to 50 nM). In the CNV model, five intravitreal injections of PEDF34 were required for therapeutic effect, whereas the mixture had a significant therapeutic effect following a single injection. Eye drops of the mixture showed significantly stronger CNV-suppressive effects than drops of PEDF34 alone. The anti-angiogenic activity of PEDF34 might be mediated by inhibition of ERK and JNK activation by VEGF, and collagen potentiated these effects.

Conclusions

Collagen can serve as a carrier and reservoir of PEDF34. PEDF peptide/collagen mixture is easy to prepare than conventional methods for maintaining the therapeutic effect of PEDF peptide.

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Acknowledgements

We would like to thank Editage (www.editage.co.kr) for English language editing.

Funding

This study was funded by the 2016 Inje University Research Grant.

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Author notes

  1. Hyun Woong Kim and Kug-Hwan Roh contributed equally to this work.

Authors and Affiliations

  1. Department of Ophthalmology, Haeundae Paik Hospital, College of Medicine, Inje University, Busan, Republic of Korea

    Hyun Woong Kim

  2. Department of Microbiology and Immunology, College of Medicine, Inje University, Busan, 47392, Republic of Korea

    Kug-Hwan Roh, Seong Wook Kim, Hana Jung, Il-Whan Choi & SaeGwang Park

  3. Department of Internal Medicine, Busan Paik Hospital, College of Medicine, Inje University, Busan, Republic of Korea

    Sung Jae Park & Na-Young Lim

  4. Paik Institute for Clinical Research, College of Medicine, Inje University, Busan, Republic of Korea

    Sung Jae Park, Na-Young Lim & SaeGwang Park

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  1. Hyun Woong Kim
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Correspondence to SaeGwang Park.

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Ethical approval

All animals were treated in accordance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. Animal experiments were examined and approved by the Institutional Animal Care and Use Committee of INJE University (Protocol No. 2016-007).

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Kim, H.W., Roh, KH., Kim, S.W. et al. Type I pig collagen enhances the efficacy of PEDF 34-mer peptide in a mouse model of laser-induced choroidal neovascularization. Graefes Arch Clin Exp Ophthalmol 257, 1709–1717 (2019). https://doi.org/10.1007/s00417-019-04394-z

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