Ultraviolet irradiation up-regulates telomerase transcription and activity in lens epithelial cells.

Purpose: Ultraviolet irradiation (UVR) increases telomerase activity in various cell types including skin, a sun-exposed organ. The lens is also continually exposed to UVR and we hypothesized that lenses exposed to UVR would have increased telomerase activity, with up-regulated TERT and TR, the two main components of the telomerase holoenzyme. To evaluate whether the cornea would protect lenses from such changes, whole globes, as well as isolated lenses, were exposed to UVR, and lenses were evaluated for changes in telomerase activity.

Methods: There were three parts to this project. The first part of this experiment evaluated freshly harvested normal adult canine lenses exposed to 0, 300, 600, or 1200 J/m(2) UVR, and then allowed to recover for 1, 2, 3 and 4 h. Since only 600 J/m(2) UVR increased telomerase activity, four more postexposure recovery time-points for this UVR dose were evaluated: 10 min, 30 min, 8 h and 24 h. The second part of this experiment used freshly enucleated whole canine globes exposed to 0, 50, 100, 150, 300, 600 or 1200 J/m(2) and incubated overnight; lens epithelial cells (LEC) were evaluated for telomerase activity. The third part evaluated lenses that were exposed to 0 or 600 J/m(2) UVR, and then allowed to recover for 8 and 24 h, before TERT and TR mRNA levels were measured.

Results: Isolated lenses exposed to 600 J/m(2) UVR had significantly higher telomerase activity than unexposed controls and other UVR doses, at all time-points except 24 h postexposure. Lenses from whole globes exposed to UVR showed a dose-dependent increase in telomerase activity except at 50 J/m(2) and 1200 J/m(2). Isolated lenses exposed to 600 J/m(2) UVR and then allowed to recover for 8 and 24 h significantly up-regulated TERT and TR mRNAs compared to unexposed control lenses.

Conclusions: Telomerase activity is regulated at both the transcriptional and post-translational levels in canine LEC. Previous work in our laboratory showed dose, time, and age-dependent changes in telomerase activity in the lens. The present study showed that TERT and TR mRNA transcription was increased for up to 24 h following an acute dose of UVR. Both telomerase activity and TERT and TR mRNA levels were elevated until 24 h post-UVR exposure, TERT in combination with TR functions in proliferation-related telomerase activity, but TERT alone has an anti-apoptotic function and its up-regulation may protect LEC from the acute effects of UVR. We are continuing to evaluate the mechanisms by which telomerase is regulated in normal and cataractous LEC.