Tumour, but not Age-associated, Increase of Senescence Markers γH2AX and p21 in the Canine Eye

Senescent cells display an irreversible cell cycle arrest with resistance to apoptosis. They are known to accumulate with age in mice, monkeys and man, and are suspected to drive the development and progression of neoplasia. Eyes develop age-associated changes, most commonly in the retina, cornea and lens. The aim of this study was to test whether senescent cells increase with age in the canine eye in general and in the microenvironment of ocular tumours in particular. The senescence markers γH2AX and p21 were tested in young (n = 10, age ≤2 years) versus old (n = 9, age range 9.5-12.4 years) canine eyes, as well as in the microenvironment of intraocular tumours, namely uveal melanocytomas (n = 13) and ciliary body adenomas (n = 9). To consider a potential association of senescence with biological behaviour, we compared the expression of both markers in tumour cells of benign uveal melanocytomas (n = 13) versus malignant conjunctival melanomas (n = 7). Canine eyes showed no age-dependent changes in senescent cells. However, a significant increase of the percentage of γH2AX- or p21-labelled cells was found in the retina, uvea and lens of tumour-bearing eyes. Tumour cells in conjunctival melanomas had a significantly increased percentage of p21-expressing cells compared with uveal melanocytomas. We conclude, that senescent cells do not accumulate with age in otherwise normal canine eyes and that a senescent microenvironment of intraocular tumours is unlikely to be age driven. In addition, as in man, the percentage of p21-positive cells was increased in melanomas, supporting the theory that malignant tumours may override the senescence-associated cell cycle arrest.