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David A Ammar, Dinesh Goswami, Kathryn Pate, Mark Lake, Rama Kant, Sharon Lake, Neera Tewari-Singh; Supersaturated Oxygen Emulsion for Healing Chemical Ocular Injury. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4363.
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The incidence of battlefield ocular trauma will likely continue to rise due to the nature of modern warfare and the increased use of improvised chemical weapons. These injuries are associated with poor prognoses due in part to the onset of Limbal Stem Cell Deficiency, leaving patients with few effective treatment options. Creating early therapies that can maintain tissue viability is therefore critical. Since oxygen plays a vital role in dermal preservation and wound healing, we have developed a topically ocular therapy that delivers oxygen to treat ocular trauma due to exposure to warfare agents like chloropicrin (CP), employed during World War I.
The therapy derives from a liquid supersaturated oxygen emulsion (SOE) wound-healing technology (DARPA), reformulated for ocular use. Oxygen levels in the emulsion and tissues treated with the SOE were evaluated using a micro-sensor. Studies were carried out in primary human corneal epithelial cells (HCEC) following 30 min exposure to 50 µM CP with and without SOE (30 and 55%) treatment. Wound closure and cell viability were assayed at 2h and 24h post-SOE exposure, respectively. Western blot analysis was assessed 24h post CP exposure. We have also used an ex vivo model using rabbit corneas exposed to CP (200nmol) for 2h. After washing, tissue was cultured for 24h with and without SOE.
Application of the SOE caused a 1.5-fold increase in HCEC viability and a 1.4-fold increase in wound closure within 2 h post-application. Additionally, studies in HCEC indicate application of the SOE caused a complete reversal in CP-induced p53 and H2A.X phosphorylation (DNA damage markers) and CP-induced increases in apoptotic cell death marker, cleaved Poly (ADP- ribose) polymerase.
Preliminary data indicates that the SOE enhances cell viability and wound (scratch) healing without causing DNA damage or apoptosis. Efficacy study also shows that the SOE causes a strong reversal in the DNA damage and cell death markers. These cell culture studies indicate that supplemental oxygenation accelerates tissue preservation and wound repair. This is especially important in a mostly avascular tissue like the cornea, and delicate cell populations such as in the limbus. Further studies examining the application of the SOE in ex vivo and in vivo corneal injury rabbit models are warranted.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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