Telomere attrition in lens epithelial cells - a target for N-acetylcarnosine therapy
Mark A. Babizhayev 1,2, Yegor E. Yegorov3
1
Innovation Vision Products, Inc., 3511 Silverside Road, Suite 105, County of New Castle, Delaware, USA 19810, 2Moscow Helmholtz Research Institute of Eye Diseases, Str. Sadovaya-Chernogryazskaya 14/19, Moscow 103064, Russian Federation, 3Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 32 Vavilov street, Moscow, 119991, Russian Federation
TABLE OF CONTENTS
- 1. Abstract
- 2. Introduction
- 3. N-acetylcarnosine and telomere shortening in human lens cells
- 3.1. Lens cellular structures
- 3.2. Peroxide threat and cellular signaling
- 3.3. Telomeres structures
- 3.4. Oxidative insult and cataract
- 3.5. Oxidative stress, the replicative lifespan of cells, telomere integrity and cellular senescence
- 3.6. Telomeres and Telomerase Activity in Lens Epithelial Cells of Normal and Cataractous Lenses
- 3.7. N-acetylcarnosine as a therapeutic tool to manage age-related cataracts in human eyes or visually disabling eye diseases as well as systemic health conditions
- 3.8. Intraocular transcorneal and systemic absorption of L-carnosine from N-acetylcarnosine ocular drug delivery system: Suitable molecular therapeutic interventions and visual sensory signaling responses
- 3.9. Human Lens Telomeres as a Prospective Biological Target for N-acetylcarnosine Ophthalmic Indications
- 3.10. The clinical effects of N-acetylcarnosine ophthalmic prodrug through protections from telomere attrition and shortening: prevention and reversal of cataracts, basic preventive health care
- 3.11. Prevention of complications of cataract surgery with N-acetylcarnosine ophthalmic prodrug: targeting secondary cataracts through modulation of cell senescent behavior
- 3.11.1. Secondary cataracts (Posterior Capsular Opacification) and their treatments
- 3.11.2. Treatment for Posterior Capsular Opacification
- 4. Summary and perspective
- 5. Acknowledgements
- 6. References
1. ABSTRACT
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 oxidative stress in the lack of efficient antioxidant lens protection. The data of visual functions (visual acuity, glare sensitivity) in older adult subjects and older subjects with cataract treated with 1% N-acetylcarnosine lubricant eye drops showed significant improvement as compared, by contrast with the control group which showed generally no improvement in visual functions, with no difference from baseline in visual acuity and glare sensitivity readings. Prevention of cellular senescence with ophthalmic prodrug N-acetylcarnosine may be a novel therapeutic target in a management of cataract, basic preventive health care and in arresting of after-cataract following extracapsular cataract extraction.
