Abstract
Purpose :
The precise etiology of keratoconus (KC) remains undetermined, despite indications that both genetic and environmental factors contribute to susceptibility. Further, the lack of an animal model for KC limits studies to in vitro methods, ex vivo donor corneas, or clinical observations. Prior studies have identified ultraviolet radiation (UVR) as a risk factor for KC, and exposure in mice and rabbits have shown KC-like phenotypes. We hypothesize that exposing C57Bl/6J mice to a controlled dose of UVR will mimic the environmental conditions that contribute to KC and induce central corneal thinning, cone-like protrusion, stromal thinning, and scarring consistent with KC.
Methods :
C57Bl/6J mice (n=9, 5 male /4 female) were exposed to UVR in a specialized chamber for controlled dosage and uniform exposure of a combination of 42% UVA and 58% UVB, was administered at a dose of 3,305 J/m2 three times per week, for six weeks. Ten mice (5 male/ 4 female) from the same litter served as untreated controls. Routine observations were made via high resolution imaging and slit lamp biomicroscopy. Corneal thickness and curvature were observed and measured via spectral domain optical coherence tomography before and after the course of treatment. Following UVR exposure, eyes from the treated and non-treated mice were collected for hematoxylin & eosin staining, sections were visualized using brightfield microscopy.
Results :
All UVR-treated mice demonstrated mild-to severe corneal [YL1] bulging and stromal haze, with females developing these characteristics sooner. Cone-like protrusions of the cornea (n=4, 2 male/2 female) were grossly observed as soon as 4 weeks. Corneal hydrops developed by four weeks in one female mouse. Ocular damage caused by UV irradiation varied in severity, though corneal edema, neovascularization, cataracts, and ocular surface abrasions were noted.
Conclusions :
With the role of UVR as an environmental risk factor for KC, it is feasible that it may be used as a method to induce keratoconus-like phenotypes in an animal model. However, an important consideration in regard to KC pathogenesis is the important role of genetic influences. Here, we were able to induce some morphological similar to KC in wild-type mice. The work presented here provides a framework for further animal models to combine the influence of UVR with KC-associated genetic backgrounds to develop a robust animal model for KC.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.