British anti-Lewisite (BAL) reduces the severity of systemic and local responses of the eye after exposure to the chemical warfare agent surrogate for Lewisite, phenylarsine oxide (PAO)

TL;DR

This study shows that BAL, when used as an eye drop, can effectively reduce eye damage and save lives after exposure to a chemical warfare agent similar to Lewisite.

Contribution

The study demonstrates BAL's efficacy as a topical treatment for ocular arsenical exposure, an unmet medical need.

Findings

BAL strongly binds to arsenic but not to essential minerals like calcium and zinc.

1% BAL eye drops significantly reduced PAO-induced ocular damage and saved all treated mice within 48 hours.

Histology showed better retinal preservation in BAL-treated mice compared to untreated ones.

Abstract

Arsenical ocular toxicity is acute, painful, and aggressive. Although British anti-Lewisite (BAL) is an approved therapy for systemic arsenical toxicity, remedial measure for ocular exposure of arsenicals is still an unmet need. This study evaluated the efficacy of BAL as topical drop for ameliorating the pathogenesis incited by phenylarsine oxide (PAO, surrogate for lewisite), a chemical warfare agent. The binding of BAL to arsenic and calcium and zinc, two essential cellular minerals was determined using Isothermal Titration Calorimetry (ITC). Ex vivo, mouse corneas were tested with various concentrations of BAL (0.1 %, 1 %, and 5 %). Injury was induced ex vivo using PAO, 25 µg/5 µL, and rescue was evaluated with 1 % BAL. In-vivo, injury to mouse cornea was induced with PAO 100 µg/5 µL and rescue was evaluated by 1 % BAL. All eyes were assessed for physical symptoms by examination under slit lamp biomicroscope, anterior segment optical coherence tomography (AS-OCT), corneal thickness, and histopathological changes. BAL bonded strongly with arsenic but negligibly with calcium and zinc. Ex-vivo cornea, response with 1 % BAL was graded superior to higher concentration. One of eight mice with PAO injury survived versus all survivals in the PAO+BAL group after injury. Topical use of BAL mitigated the exacerbated ocular response exhibited by PAO injury. Histology revealed better preservation of retinal architecture in BAL treated mice. 1 % BAL alleviates PAO induced fatality in mice. The rescue in the posterior segment pathogenesis was remarkable. BAL is a promising decontaminant for ocular arsenical exposure and warrants further investigation.

•Evaluated the efficacy of BAL as an eye drop in a murine model for ameliorating the pathogenesis incited by phenyl arsine oxide (PAO).•Assessments included histopathology as well as eye examinations under slit lamp biomicroscope and anterior segment optical coherence tomography (AS-OCT).•The results indicated that BAL is a promising decontaminant for ocular surface injury caused by arsenical exposure.•Histology revealed better preservation of retinal architecture in BAL treated mice.•PAO induced fatality in 87.5 % of mice in 48 h. With 1 % BAL eye drop, all mice survived 48 h.

Evaluated the efficacy of BAL as an eye drop in a murine model for ameliorating the pathogenesis incited by phenyl arsine oxide (PAO).

Assessments included histopathology as well as eye examinations under slit lamp biomicroscope and anterior segment optical coherence tomography (AS-OCT).

The results indicated that BAL is a promising decontaminant for ocular surface injury caused by arsenical exposure.

Histology revealed better preservation of retinal architecture in BAL treated mice.

PAO induced fatality in 87.5 % of mice in 48 h. With 1 % BAL eye drop, all mice survived 48 h.

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