Ultraviolet Radiation-Induced Corneal Degeneration in 129 Mice

Abstract

Ultraviolet radiation (UVR) is a risk factor for the development of ocular disease in humans, including acute photokeratitis, chronic corneal spheroidal degeneration, and cataract formation. This report describes the ocular lesions seen in 21 mice chronically exposed to UVR as part of a skin carcinogenicity study. All globes were affected to varying degrees. The primary lesion, not previously reported in UVR-exposed mice, was marked loss of keratocytes relative to age-matched controls. Secondary lesions included corneal stromal thinning, keratoconus, corneal vascularization and fibrosis, keratitis, globe rupture, and phthisis bulbi. In addition, more than 90% of UVR-exposed and unexposed lenses had evidence of cataract formation; this is the first report of the occurrence of spontaneous cataracts in 129 mice. In a subsequent study, apoptotic cells were identified histologically and by cleaved caspase 3 immunoreactivity in the corneal epithelium and, less commonly, in the corneal stroma after acute UVR exposure. Based on this finding, we propose that the loss of keratocytes observed in the chronic study was due to UVR-induced apoptosis.

The Epidemiology and Etiology of Keratoconus

“…92 This is thought to trigger what is referred to as a cascade of events leading to KC, such as an alteration of various corneal proteins, increased enzyme activities and apoptotic cell death. 91 Moreover, animal models of apoptosis as a result of exposure to ultraviolet radiation in rabbit cornea 93 and loss of keratocytes and subsequent corneal stromal thinning in mice 94 support the possibility of sun exposure as a risk factor for KC in genetically susceptible individuals. The human cornea has a high incidence of acquired chromosome abnormalities in the keratocyte tissue.…”

Apoptosis in Rat Cornea After In Vivo Exposure to Ultraviolet Radiation at 300 nm

“…We therefore believe that the TUNEL staining in our study represents apoptotic cells. The recognition of corneal sterile keratolysis 120 hours after exposure is essential to interpret UVR-induced changes and agrees with the study by Newkirk et al 21 Excessive or inappropriate metalloproteinase (MMP) activity is the primary mechanism of sterile keratolysis. 22 UVR has been shown to induce the production of MMP by corneal cells.…”

The First Successful Hand-Rearing of a Neonate Hawaiian Monk Seal (Monachus schauinslandi) and Post-Release Management Challenges

“…Multiple environmental risk factors likely predisposed this animal to corneal disease. These factors include UV light exposure (Kennedy et al, 1997;Newkirk et al, 2007;Doughty & Cullen, 2008) and water quality parameters (nitrate spikes, fluctuating salinity, and spikes in bacteria levels). After the gradual onset of the condition in the unnatural environment (the rehabilitation enclosure/pool), the edema regressed in the natural environment (shoreline pen) after several weeks.…”