Telomere attrition in lens epithelial cells - a target for N-acetylcarnosine therapy.

@article{Babizhayev2010TelomereAI,
  title={Telomere attrition in lens epithelial cells - a target for N-acetylcarnosine therapy.},
  author={M. Babizhayev and Y. Yegorov},
  journal={Frontiers in bioscience},
  year={2010},
  volume={15},
  pages={
          934-56
        }
}
The lens epithelium is especially vulnerable to oxidative stress. The erosion and shortening of telomeres in human lens epithelial cells in the lack of telomerase activity has been recognized as a primary cause of premature lens senescence phenotype that trigger human cataractogenesis. Carnosine, released ophthalmically from N-acetylcarnosine prodrug lubricant eye drops , at physiological concentration might remarkably reduce the rate of telomere shortening in the lens cells subjected to… Expand
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References

SHOWING 1-10 OF 189 REFERENCES
Revival of the Lens Transparency with N-Acetylcarnosine
The risk, cost and social requirement factors drive the investigation of pharmaceutical approaches to the management of cataracts. The role of free-radical-induced lipid oxidation (LPO) in theExpand
Telomerase activity in lens epithelial cells of normal and cataractous lenses.
TLDR
Telomerase activity is likely important in the germinative epithelium to maintain its proliferative potential and prevent cell senescence and 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 cellsenescence. Expand
Effects of lipid peroxidation products on the rat lens in organ culture: a possible mechanism of cataract initiation in retinal degenerative disease.
Rat lenses in organ culture which are exposed to bovine rod outer segments (ROS) or to the major fatty acid of ROS, docosahexaenoic acid, are impaired in their ability to accumulate radiolabeledExpand
Vitamin C mediates chemical aging of lens crystallins by the Maillard reaction in a humanized mouse model
TLDR
Data strongly implicate vitamin C in lens crystallin aging and may serve as a model for protein aging in other tissues particularly rich in vitamin C, such as the hippocampal neurons and the adrenal gland. Expand
Lipid peroxidation and cataracts: N-acetylcarnosine as a therapeutic tool to manage age-related cataracts in human and in canine eyes.
TLDR
N-acetylcarnosine (as the ophthalmic drug Can-C), has been found to be suitable for the nonsurgical prevention and treatment of age-related cataracts and in a recent clinical trial it was shown to produce an effective, safe and long-term improvement in sight. Expand
Prevention of selenite-induced cataractogenesis by acetyl-L-carnitine: an experimental study.
TLDR
Data suggest that ALCAR is able to significantly retard experimental selenite-induced cataractogenesis. Expand
[Role of lipid peroxidation in pathogenesis of senile cataract].
TLDR
The lens structure changes caused by lipid peroxidation can, with other risk factors present, influence the occurrence and development of mature cataract. Expand
Vitex negundo attenuates calpain activation and cataractogenesis in selenite models.
TLDR
Results indicate good antioxidant and therapeutic potential of FVN in modulating biochemical parameters against selenite-induced cataract, which have been reported in this paper for the first time. Expand
Oxidative Stress Markers in Aqueous Humor of Patients with Senile Cataracts
TLDR
Significant increases in the levels of SOD activity and total protein correlated with the severity of the cataract but not with patient age, suggesting that progressed cataracts is associated with molecules leaking from the lens capsule. Expand
hTERT extends proliferative lifespan and prevents oxidative stress-induced apoptosis in human lens epithelial cells.
TLDR
The human telomerase reverse transcriptase (hTERT) catalytic subunit was introduced into HLECs and has supported normal growth after 48 population doublings to date and also enhanced antiapoptotic activity against oxidative stress. Expand
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