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Exp Eye Res. 2021 Dec 23;215:108908. doi: 10.1016/j.exer.2021.108908. Epub 2021 Dec 23.

Intravitreal administration of recombinant human opticin protects against hyperoxia-induced pre-retinal neovascularization.

Experimental eye research

Izabela P Klaska, Anne White, Pilar Villacampa, Justin Hoke, Laura Abelleira-Hervas, Ryea N Maswood, Robin R Ali, Catey Bunce, Richard D Unwin, Garth J S Cooper, Paul N Bishop, James W Bainbridge

Affiliations

  1. UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London, EC1V 9EL, UK; KCL Centre for Cell and Gene Therapy, Tower Wing, Guy's Hospital, Great Maze Pond, London, SE1 9RT, UK.
  2. Division of Evolution & Genomic Sciences, School of Biological Sciences, FBMH, University of Manchester, Manchester, UK.
  3. UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London, EC1V 9EL, UK; Josep Carreras Leukaemia Research Institute, Ctra de Can Ruti, Barcelona, Spain.
  4. UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London, EC1V 9EL, UK.
  5. School of Population Health and Environmental Sciences, Faculty of Life Sciences and Medicine, King's College London, Addison House, London, SE1 1UL, UK.
  6. Division of Cardiovascular Sciences, School of Medical Sciences, FBMH, University of Manchester, Manchester, UK; Stoller Biomarker Discovery Centre and Division of Cancer Sciences, School of Medical Sciences, FBMH, University of Manchester, Manchester, UK.
  7. Division of Cardiovascular Sciences, School of Medical Sciences, FBMH, University of Manchester, Manchester, UK.
  8. Division of Evolution & Genomic Sciences, School of Biological Sciences, FBMH, University of Manchester, Manchester, UK; Manchester Royal Eye Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
  9. UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London, EC1V 9EL, UK. Electronic address: [email protected].

PMID: 34954204 DOI: 10.1016/j.exer.2021.108908

Abstract

Opticin is an extracellular glycoprotein present in the vitreous. Its antiangiogenic properties offer the potential for therapeutic intervention in conditions such as proliferative diabetic retinopathy and retinopathy of prematurity. Here, we investigated the hypothesis that intravitreal administration of recombinant human opticin can safely protect against the development of pathological angiogenesis and promote its regression. We generated and purified recombinant human opticin and investigated its impact on the development and regression of pathological retinal neovascularization following intravitreal administration in murine oxygen-induced retinopathy. We also investigated its effect on normal retinal vascular development and function, following intravitreal injection in neonatal mice, by histological examination and electroretinography. In oxygen-induced retinopathy, intravitreal administration of human recombinant opticin protected against the development of retinal neovascularization to similar extent as aflibercept, which targets VEGF. Opticin also accelerated regression of established retinal neovascularization, though the effect at 18 h was less than that of aflibercept. Intravitreal administration of human recombinant opticin in neonatal mice caused no detectable perturbation of subsequent retinal vascular development or function. In summary we found that intraocular administration of recombinant human opticin protects against the development of pathological angiogenesis in mice and promotes its regression.

Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.

Keywords: Angiogenesis; Neovascularization; OIR; Opticin; PDR; ROP

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