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Chengxin Zhou, Fengyang Lei, Nathan Scott, Vassiliki Kapoulea, Marie-Claude Robert, James Chodosh, Claes H Dohlman, Eleftherios I Paschalis; The Mechanism of Retinal Damage Following Ocular Surface Burn with Alkali. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5892.
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© ARVO (1962-2015); The Authors (2016-present)
Alkali burns to the eye constitute a leading cause of worldwide corneal blindness. We recently showed that alkali burns may also cause retinal and optic nerve damage and subsequent irreversible vision loss. This study investigates the physical, biochemical, and immunological components of retinal damage after corneal alkali burns and explores a novel neuroprotective therapy.
Mice (C57BL/6 and TNF receptor 1/2 knock-out) and Dutch belted pigmented rabbits received central corneal burns using sodium hydroxide. The burned eyes were subsequently irrigated with saline for 15 minutes. Some C57BL/6 mice and rabbits were implanted with pH, redox, and oxygen micro-sensors in the anterior and posterior segments of the eye prior to corneal alkali burn. The in vivo measurements were performed for 26 hours. Intraocular pressure (lOP) measurements were performed on mice and rabbits terminally using a microelectromechanical pressure transducer in the anterior chamber. Tissues were collected at different pre-specified time points. Ocular inflammation was assessed with qPCR, in situ hybridization, Western Blot, and flow cytometry. Retinal damage and protection was assessed using in situ cell death detection assay and immunohistochemistry.
In vivo pH, O2 and redox measurements showed that alkali is effectively buffered by the anterior segment with no direct penetration to the posterior segment. Rather, acute pH, O2 and redox changes in the anterior chamber caused profound uveal inflammation and subsequent release of pro-inflammatory cytokines posteriorly. In burned eyes, TNF-α mRNA expression was elevated in the cornea and retina- in the latter, particularly in the ganglion cell layer, inner and outer plexiform layers. Deletion of TNF receptor genes in burned mice suppressed retinal inflammation and retinal damage. Likewise, prompt TNF-α inhibition by monoclonal antibody also suppressed retinal inflammation and damage in mice and rabbits.
This study suggests that corneal alkali burns cause retinal damage via secondary inflammation and upregulation of TNF-α expression. Alkali is well buffered by the anterior segment. Prompt TNF-α inhibition substantially protects the eye and this finding may be clinically important for the treatment of ocular burns.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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