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Sustained Subconjunctival Delivery of Infliximab Protects the Cornea and Retina Following Alkali Burn to the Eye.
- Source :
-
Investigative ophthalmology & visual science [Invest Ophthalmol Vis Sci] 2017 Jan 01; Vol. 58 (1), pp. 96-105. - Publication Year :
- 2017
-
Abstract
- Purpose: Tumor necrosis factor (TNF)-α is upregulated in eyes following corneal alkali injury and contributes to corneal and also retinal damage. Prompt TNF-α inhibition by systemic infliximab ameliorates retinal damage and improves corneal wound healing. However, systemic administration of TNF-α inhibitors carries risk of significant complications, whereas topical eye-drop delivery is hindered by poor ocular bioavailability and the need for patient adherence. This study investigates the efficacy of subconjunctival delivery of TNF-α antibodies using a polymer-based drug delivery system (DDS).<br />Methods: The drug delivery system was prepared using porous polydimethylsiloxane/polyvinyl alcohol composite fabrication and loaded with 85 μg of infliximab. Six Dutch-belted pigmented rabbits received ocular alkali burn with NaOH. Immediately after the burn, subconjunctival implantation of anti-TNF-α DDS was performed in three rabbits while another three received sham DDS (without antibody). Rabbits were followed with photography for 3 months.<br />Results: After 3 months, the device was found to be well tolerated by the host and the eyes exhibited less corneal damage as compared to eyes implanted with a sham DDS without drug. The low dose treatment suppressed CD45 and TNF-α expression in the burned cornea and inhibited retinal ganglion cell apoptosis and optic nerve degeneration, as compared to the sham DDS treated eyes. Immunolocalization revealed drug penetration in the conjunctiva, cornea, iris, and choroid, with residual infliximab in the DDS 3 months after implantation.<br />Conclusions: This reduced-risk biologic DDS improves corneal wound healing and provides retinal neuroprotection, and may be applicable not only to alkali burns but also to other inflammatory surgical procedures such as penetrating keratoplasty and keratoprosthesis implantation.
- Subjects :
- Animals
Antirheumatic Agents administration & dosage
Burns, Chemical diagnosis
Conjunctiva
Cornea metabolism
Corneal Injuries diagnosis
Corneal Neovascularization diagnosis
Corneal Neovascularization etiology
Delayed-Action Preparations
Disease Models, Animal
Drug Implants
Eye Burns chemically induced
Eye Burns diagnosis
Female
Follow-Up Studies
Rabbits
Retina drug effects
Retina metabolism
Retina pathology
Retinal Diseases diagnosis
Retinal Diseases etiology
Tumor Necrosis Factor-alpha antagonists & inhibitors
Tumor Necrosis Factor-alpha metabolism
Burns, Chemical drug therapy
Cornea drug effects
Cornea pathology
Corneal Injuries drug therapy
Corneal Neovascularization prevention & control
Eye Burns drug therapy
Infliximab administration & dosage
Retinal Diseases prevention & control
Subjects
Details
- Language :
- English
- ISSN :
- 1552-5783
- Volume :
- 58
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Investigative ophthalmology & visual science
- Publication Type :
- Academic Journal
- Accession number :
- 28114570
- Full Text :
- https://doi.org/10.1167/iovs.16-20339