Microporous Drug Delivery System for Sustained Anti-VEGF Delivery to the Eye.

Animals Corneal Neovascularization / drug therapy Drug Delivery Systems Eye Burns Rabbits Vascular Endothelial Growth Factor A / therapeutic use Vascular Endothelial Growth Factors / therapeutic use
VEGF angiogenesis avastin bevacizumab cornea inflammation neovascularization retina

Journal

Translational vision science & technology
ISSN: 2164-2591
Titre abrégé: Transl Vis Sci Technol
Pays: United States
ID NLM: 101595919

Informations de publication

Date de publication:
07 2020
Historique:
received: 27 01 2020
accepted: 04 05 2020
entrez: 29 8 2020
pubmed: 29 8 2020
medline: 29 8 2020
Statut: epublish

Résumé

To describe a novel microporous drug delivery system (DDS) for sustained anti- vascular endothelial growth factor (VEGF) delivery to the eye and to evaluate its efficacy in a corneal injury model. A macro-porous DDS (1.5 × 1.5 × 4 mm) loaded with 2 mg of bevacizumab was implanted subconjunctivally in three Dutch-belted pigmented rabbits after corneal alkali injury (2N NaOH). Three rabbits received sham DDS. Animals were followed for three months and assessed in vivo and ex vivo for corneal neovascularization (NV), epithelial defect, stromal scarring, endothelial cell loss, and expression of angiogenic and inflammatory markers in the cornea and retina. Anti-VEGF DDS treatment led to complete inhibition of superior cornea NV and complete corneal re-epithelialization by day 58 whereas sham DDS resulted in severe cornea NV and persistent epithelial defect (9%∼12% of total cornea area) through the end of the study. Histologically, anti-VEGF DDS significantly reduced CD45 Use of subconjunctival anti-VEGF DDS suppresses cornea NV, inflammation, stromal scarring, prevents endothelial cell loss, and abrogates retinal VEGF upregulation in a rabbit corneal alkali burn model. Moreover, it delivers anti-VEGF antibodies to the retina for three months. This delivery platform could enable antibody therapy of other corneal and retinal vascular pathologies. We describe a method for sustained anti-VEGF delivery to the eye for the treatment of ocular injuries.

Identifiants

DOI: 10.1167/tvst.9.8.5 PMID: 32855852 PMC: PMC7422759
pubmed: 32855852
doi: 10.1167/tvst.9.8.5
pii: TVST-20-2297
pmc: PMC7422759
doi:

Substances chimiques

Vascular Endothelial Growth Factor A 0
Vascular Endothelial Growth Factors 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Pagination

5

Subventions

Organisme : NEI NIH HHS
ID : P30 EY003790
Pays : United States

Informations de copyright

Copyright 2020 The Authors.

Déclaration de conflit d'intérêts

Disclosure: C. Zhou, None; A. Singh, None; G. Qian, None; N. Wolkow, None; C.H. Dohlman, None; D.G. Vavvas, None; J. Chodosh, None; E.I. Paschalis, (P)

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Auteurs

Chengxin Zhou (C)

Boston Keratoprosthesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear and Schepens Eye Research Institute, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.

Arushi Singh (A)

Boston Keratoprosthesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear and Schepens Eye Research Institute, Boston, MA, USA.

Grace Qian (G)

Boston Keratoprosthesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear and Schepens Eye Research Institute, Boston, MA, USA.

Natalie Wolkow (N)

Harvard Medical School, Boston, MA, USA.
David G. Cogan Laboratory of Eye Pathology and Ophthalmic Plastic Surgery Service, Massachusetts Eye and Ear Infirmary, Boston, MA, USA.

Claes H Dohlman (CH)

Boston Keratoprosthesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear and Schepens Eye Research Institute, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.

Demetrios G Vavvas (DG)

Angiogenesis Laboratory, Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA.

James Chodosh (J)

Boston Keratoprosthesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear and Schepens Eye Research Institute, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.
Disruptive Technology Laboratory (D.T.L.), Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.

Eleftherios I Paschalis (EI)

Boston Keratoprosthesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear and Schepens Eye Research Institute, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.
Disruptive Technology Laboratory (D.T.L.), Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.

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