Abstract
Absorption of UV rays by DNA generates the formation of mutagenic cyclobutane pyrimidine dimers (CPD) and pyrimidine (6–4) pyrimidone photoproducts (6-4PP). These damages are the major cause of skin cancer because in turn, they can lead to signature UV mutations. The eye is exposed to UV light, but the cornea is orders of magnitude less prone to UV-induced cancer. In an attempt to shed light on this paradox, we compared cells of the corneal epithelium and the epidermis for UVB-induced DNA damage frequency, repair and cell death sensitivity. We found similar CPD levels but a 4-time faster UVB-induced CPD, but not 6-4PP, repair and lower UV-induced apoptosis sensitivity in corneal epithelial cells than epidermal. We then investigated levels of DDB2, a UV-induced DNA damage recognition protein mostly impacting CPD repair, XPC, essential for the repair of both CPD and 6-4PP and p53 a protein upstream of the genotoxic stress response. We found more DDB2, XPC and p53 in corneal epithelial cells than in epidermal cells. According to our results analyzing the protein stability of DDB2 and XPC, the higher level of DDB2 and XPC in corneal epithelial cells is most likely due to an increased stability of the protein. Taken together, our results show that corneal epithelial cells have a better efficiency to repair UV-induced mutagenic CPD. On the other hand, they are less prone to UV-induced apoptosis, which could be related to the fact that since the repair is more efficient in the HCEC, the need to eliminate highly damaged cells by apoptosis is reduced.
Highlights
The role of UV exposure in the prevalence of sun-related cancers is well documented [1,2,3,4,5]
The quantified cyclobutane pyrimidine dimers (CPD) signal reveals that when irradiated with a given dose of UVB, 3.4 times more CPD are induced in the corneal epithelium than in the epidermis (Fig 1B)
It has been previously described that ocular region would receive between 59% and 77% of UV light reaching the top of the head [62], UV light dosimetry of the eye is a controversial matter, as many influential factors cannot be correctly compensated
Summary
The role of UV exposure in the prevalence of sun-related cancers is well documented [1,2,3,4,5]. Solar exposure causes many pathologies of the ocular surface. It is well documented that exposure to solar UV light is a proven risk factor in the incidence of pterygium, ocular surface squamous neoplasia (OSSN), climatic droplet keratopathy and actinic conjunctivitis [20,21,22,23,24]. The incidence of OSSN is 0.3 per million in the US [24] and 86% does not involve the cornea [25]. Non-melanoma skin cancer incidence is over 15 000 per million in the US [26]. The cornea shares functional and structural similarities with the skin, there is a clear difference in sensitivity to UV-induced neoplasia between corneal epithelial and epidermal cells
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