Telomerase activity in lens epithelial cells of normal and cataractous lenses

Telomerase is a ribonucleoprotein responsible for maintaining telomere leng th, preventing chromosomal degradation and recombination, and repairing DNA strand breaks. These activities are believed to be important in preventing cell senescence. Telomerase activity is normally found in germinal, neopla stic and stem cells, but not any ocular tissue studied to date. The epithel ium of the crystalline lens is comprised of a population of cells with dive rse mitotic potential including the germinative epithelium which contains c ells with the potential for unlimited replicative capacity, equatorial cell s which terminally differentiate into lens fibers, and the central epitheli um which are considered to be quiescent and nonreplicative under normal cir cumstances. We speculated that the germinative region of lens epithelial ce lls might have telomerase activity, and that dysregulation of its activity might be associated with cataractogenesis. We investigated these hypotheses in lens capsule specimens from normal and cataractous dogs and from cultures of canine lens epithelial cells using st andard assays for telomerase activity and telomere length. Telomerase activ ity was found in normal canine lens epithelial cells in the central, germin ative and equatorial regions of the anterior lens capsule at equivalent lev els. Similar findings were made in feline and murine lens epithelial cells, indicating that the presence of telomerase activity in the lens was not sp ecies specific. Lens fiber cells, corneal epithelium and endothelium and no npigmented ciliary epithelium were telomerase negative. Telomerase activity and telomere lengths were significantly greater in lens epithelia from cat aractous lenses when compared with normal lenses. Since telomerase activity is associated with an immortal phenotype, the pre sence of telomerase activity in the lens epithelial cells may function to p revent conversion to senescence. It was, therefore, difficult to explain wh y these cells cannot be passaged more than four times in culture. We found that telomerase activity and telomere lengths gradually decreased with incr eased passages until telomerase activity was no longer present at passage t wo. Consistent with these findings, there were no senescent cells present o n the lens capsule when the lens was initially dissected for culture, but a n increasing number of cells were senescent with each passage, correlating well with the loss of telomerase activity. Telomerase activity is likely important in the germinative epithelium to ma intain its proliferative potential and prevent cell senescence. Telomerase may function in the quiescent, central lens to maintain telomeres damaged b y oxidative stress and ultraviolet light exposure, thereby preventing accel erated loss of these elements which triggers cell senescence, It remains to be determined if the increase in telomerase activity in lens epithelial ce lls from cataractous lenses is a primary dysregulation that may have a role in the development of the cataract, or is secondary to cataract formation. (C) 1999 Academic Press.