Telomerase activity in lens epithelial cells of normal and cataractous lenses. 1999

C M Colitz, and M G Davidson, and M C McGAHAN
Companion Animal and Special Species Medicine, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC, 27606, USA.

Telomerase is a ribonucleoprotein responsible for maintaining telomere length, 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, neoplastic and stem cells, but not any ocular tissue studied to date. The epithelium of the crystalline lens is comprised of a population of cells with diverse mitotic potential including the germinative epithelium which contains cells with the potential for unlimited replicative capacity, equatorial cells which terminally differentiate into lens fibers, and the central epithelium which are considered to be quiescent and nonreplicative under normal circumstances. We speculated that the germinative region of lens epithelial cells 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 standard assays for telomerase activity and telomere length. Telomerase activity was found in normal canine lens epithelial cells in the central, germinative and equatorial regions of the anterior lens capsule at equivalent levels. Similar findings were made in feline and murine lens epithelial cells, indicating that the presence of telomerase activity in the lens was not species specific. Lens fiber cells, corneal epithelium and endothelium and nonpigmented ciliary epithelium were telomerase negative. Telomerase activity and telomere lengths were significantly greater in lens epithelia from cataractous lenses when compared with normal lenses. Since telomerase activity is associated with an immortal phenotype, the presence of telomerase activity in the lens epithelial cells may function to prevent conversion to senescence. It was, therefore, difficult to explain why these cells cannot be passaged more than four times in culture. We found that telomerase activity and telomere lengths gradually decreased with increased passages until telomerase activity was no longer present at passage two. Consistent with these findings, there were no senescent cells present on the lens capsule when the lens was initially dissected for culture, but an 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 maintain its proliferative potential and prevent cell senescence. Telomerase may function in the quiescent, central lens to maintain telomeres damaged by oxidative stress and ultraviolet light exposure, thereby preventing accelerated loss of these elements which triggers cell senescence. It remains to be determined if the increase in telomerase activity in lens epithelial cells from cataractous lenses is a primary dysregulation that may have a role in the development of the cataract, or is secondary to cataract formation.

UI MeSH Term Description Entries
D007908 Lens, Crystalline A transparent, biconvex structure of the EYE, enclosed in a capsule and situated behind the IRIS and in front of the vitreous humor (VITREOUS BODY). It is slightly overlapped at its margin by the ciliary processes. Adaptation by the CILIARY BODY is crucial for OCULAR ACCOMMODATION. Eye Lens,Lens, Eye,Crystalline Lens
D011817 Rabbits A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes. Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
D002386 Cataract Partial or complete opacity on or in the lens or capsule of one or both eyes, impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). (Dorland, 27th ed) Cataract, Membranous,Lens Opacities,Pseudoaphakia,Cataracts,Cataracts, Membranous,Lens Opacity,Membranous Cataract,Membranous Cataracts,Opacities, Lens,Opacity, Lens,Pseudoaphakias
D002415 Cats The domestic cat, Felis catus, of the carnivore family FELIDAE, comprising over 30 different breeds. The domestic cat is descended primarily from the wild cat of Africa and extreme southwestern Asia. Though probably present in towns in Palestine as long ago as 7000 years, actual domestication occurred in Egypt about 4000 years ago. (From Walker's Mammals of the World, 6th ed, p801) Felis catus,Felis domesticus,Domestic Cats,Felis domestica,Felis sylvestris catus,Cat,Cat, Domestic,Cats, Domestic,Domestic Cat
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D002455 Cell Division The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION. M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D003584 Cytological Techniques Methods used to study CELLS. Cytologic Technics,Cytological Technic,Cytological Technics,Cytological Technique,Technic, Cytological,Technics, Cytological,Technique, Cytological,Techniques, Cytological,Cytologic Technic,Technic, Cytologic,Technics, Cytologic
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D004847 Epithelial Cells Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells. Adenomatous Epithelial Cells,Columnar Glandular Epithelial Cells,Cuboidal Glandular Epithelial Cells,Glandular Epithelial Cells,Squamous Cells,Squamous Epithelial Cells,Transitional Epithelial Cells,Adenomatous Epithelial Cell,Cell, Adenomatous Epithelial,Cell, Epithelial,Cell, Glandular Epithelial,Cell, Squamous,Cell, Squamous Epithelial,Cell, Transitional Epithelial,Cells, Adenomatous Epithelial,Cells, Epithelial,Cells, Glandular Epithelial,Cells, Squamous,Cells, Squamous Epithelial,Cells, Transitional Epithelial,Epithelial Cell,Epithelial Cell, Adenomatous,Epithelial Cell, Glandular,Epithelial Cell, Squamous,Epithelial Cell, Transitional,Epithelial Cells, Adenomatous,Epithelial Cells, Glandular,Epithelial Cells, Squamous,Epithelial Cells, Transitional,Glandular Epithelial Cell,Squamous Cell,Squamous Epithelial Cell,Transitional Epithelial Cell

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