Multimodal imaging of the biphasic corneal wound healing response to topical acrolein exposure

Abstract

Purpose : Acrolein (Acr) is an aldehyde that is used in a variety of manufacturing processes, as a chemical feedstock for the generation of acrylic acid and other organic chemicals, and as a biocide for clearing waterways. Notably, Acr was previously used as a chemical warfare agent, contributing to its listing as a chemical of concern due to the risk of accidental spillage or use by terrorists. Given the potential for exposure to acrolein, this study aimed to characterize ocular changes induced by topical Acr exposure through longitudinal monitoring of corneal response with multimodal imaging.

Methods : Following an IACUC-approved protocol, a murine model of ocular Acr exposure at 2.5 mg/mL for 30s was performed. Anterior segment optical coherence tomography, OCT angiography, slit lamp biomicroscopy, and in vivo corneal confocal microscopy (IVCM) were performed prior to the injury and up to 84 days after. Eyes were enucleated for histological assessment following day 84.

Results : Topical Acr exposure resulted in acute swelling and strong opacity at 3d, which would largely recover by 7d. A low degree of opacity remained through 21d, after which swelling and opacity began to increase, worsening through to 84d. Neovascularization was observed around 14d, remaining largely unchanged at 21d, before becoming more intense while spreading into the central cornea at 42d and 84d. IVCM demonstrated irregular cell morphology in the epithelium at 3d that returned to normal by 7-14d. The stroma showed immune cell infiltration and signs of keratocyte apoptosis at 3-7d, with hyperreflective deposits of fiber-like structures, possibly indicative of fibrosis, seen as early as 21d. Acr-exposed eyes also presented with significantly enlarged and altered endothelial cells, an adaptive response to endothelial cell loss.

Conclusions : We demonstrated the biphasic nature of Acr injury in the cornea, consisting of an acute and chronic phase and unique among other chemical injuries such as alkali burn. The acute phase is characterized by early inflammation with corneal edema and opacity that largely recovers within the first week yet does not completely resolve. Additionally, limited peripheral corneal neovascularization can be seen. The chronic phase, beginning after three weeks, presents with increased neovascularization propagating into the central cornea and the recurrence of corneal opacity and swelling accompanied by fibrosis.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.