Abstract
Purpose :
Despite the implementation of protective measures, radiation keratopathy remains a prevalent complication, causing blinding corneal complications. This study aimed to establish a novel mouse model of radiation keratopathy to characterize the pathophysiology of the disease and enable future identification of potential treatments.
Methods :
The study was conducted in compliance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research, it was approved by the ACUC at University of Illinois at Chicago.Thirty-six male six-week mice were divided equally into six groups, and the right eye was irradiated using X-Rad 320 irradiation unit (PRECISION, North Branford, USA) with 5.00, 10.00, 15.00, 20.00, 25.00, and 30.00 Gray of X-ray radiation (Figures 1A,1B). The mice were observed on the first day, followed by weekly for one month and thereafter monthly for one year using the slit-lamp. During final follow-up, anterior segment OCT was conducted, and subsequently, all mice were euthanized. The corneal sections were stained with hematoxylin and eosin, β-galactosidase, CK12, and β-III tubulin.
Results :
Corneal neovascularization and opacity showed a dose-dependent increase with an increase in radiation dose. Histopathologically, the increasing radiation led to an expansion in the number of goblet cells and conjunctival cells covering the cornea, as well as stromal fibrosis compatible with less expression of CK12 in immunostaining. A dose-dependent increase in β-galactosidase staining highlights increased cellular senescence. A more pronounced decrease in nerve elongation within the sub-basal nerve plexus was observed correlating with escalating doses of radiation. Central corneal thickness showed a decreasing trend with increasing radiation dosage.(Figure 2)
Conclusions :
This study presents a suitable model of radiation keratopathy. In-depth analysis revealed that higher doses of radiation are associated with increased cellular senescence, a disruption in the differentiation of epithelial cells, and notable deterioration in the morphology and organization of corneal nerve fibers.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.