n-acetylcarnosine and Eye-Diseases

The latest estimates of the World Health Organization indicate that there are 161 million visually impaired individuals worldwide, 37 million of whom are blind, with a yearly increase of 1-2 million. The scientists developed and patented the lubricant eye drops formulated as 1%N-acetylcarnosine prodrug of l-carnosine containing a mucoadhesive cellulose-based compound combined with corneal absorption promoters in an ocular drug delivery system. Carcinine is suitable for the systemic administration (per oral) for ophthalmic therapeutic indications. The HPLC analysis was developed to search the pathways of ocular metabolic activities of 1%N-acetylcarnosine and the bioactivation of this drug molecule promoting transcorneal uptake of l-carnosine in the aqueous humor. A meta-analysis of phase 2 randomized double-blind placebo-controlled clinical trial data was conducted. The intraocular absorbed l-carnosine demonstrated a number of pharmacological mechanisms of prevention and reversal of cataracts. Results of systemic absorption of l-carnosine provide tuberomammillary activation that regulates neuronal functions such as hypothalamic control promoting sensory input in the primary vision perceptual pathway. The parabulbar, subconjunctival, and intravitreal injection of carcinine with most of the vehicle removed is not toxic to intraocular structures, reduces postoperative intraocular inflammation, is a potentially useful tool in the treatment of proliferative vitreoretinopathy as well as considered as the antiapoptotic drug for the protection of photoreceptor cells from oxidative light-induced stress. The discovery of naturally occurring carnosine derivatives introduces N-acetylcarnosine and carcinine as effective medical treatment for sight-threatening eye disorders.

Topics: Administration, Ophthalmic; Animals; Carnosine; Cataract; Chromatography, High Pressure Liquid; Clinical Trials, Phase II as Topic; Drug Delivery Systems; Eye Diseases; Humans; Prodrugs; Randomized Controlled Trials as Topic; Vitreoretinopathy, Proliferative

The purpose of this study was to determine how the naturally occurring molecules N-acetylcarnosine, L-carnosine, and carcinine, which are chemical or pharmacological chaperones, affect the cells and biomolecules of patients with skin diseases, cosmetic skin lesions, or underlying clinically significant visual impairment such as age-related cataracts, age-related retinal degeneration, and ocular complications of diabetes. We evaluated and characterized the effects of cited pharmacological chaperones on enzyme activity, protein structure in tissues, and other biomarkers of diseases in skin cells and tissues or in ocular tissues (human cataractous and normal lenses) derived from ophthalmic patients or age-matched donors. The samples were used to test imidazole-containing peptidomimetic chemical/pharmacological chaperones in relation to oxidative stress induced by reaction with lipid peroxides or advanced non-enzymatic glycation processes. Chaperone function is characterized by interaction with other proteins, mediating their folding, transport, and interaction with other molecules, lipid peroxidation products, and membranes. Although these therapies remain on hold pending further investigation, we present growing evidence demonstrating the ability of N-acetylcarnosine (lubricant eye drops) or carcinine pharmacological chaperone therapy to act as novel treatments for age-related cataracts, age-related macular degeneration, and ocular complications of diabetes. Finally, we examine strategies for identifying potential chaperone compounds and for experimentally demonstrating chaperone and transglycating (de-glycation) types of activity in in vitro and in vivo models of human age-related eye diseases, such as cataracts, and advanced glycation tissue protein-engineered systems.

Topics: Aging; Animals; Biomarkers; Carnosine; Chemistry, Pharmaceutical; Chronic Disease; Drug Carriers; Drug Compounding; Drug Design; Eye Diseases; Glycation End Products, Advanced; Humans; Lens, Crystalline; Lipid Peroxidation; Models, Molecular; Molecular Structure; Oxidative Stress; Skin; Skin Aging; Skin Diseases; Structure-Activity Relationship

This review article explores the functional activity and development aspects of N-acetylcarnosine for the visual system as revealed by the use of a variety of biophysical, physiological and therapeutic ophthalmic methods. It is designed for pharmacists and more advanced ophthalmology, optometry and pharmacology researchers who wish to gain a basic understanding of the biological effects of N-acetylcarnosine for vision and to share in the excitement of the latest developments in this field. Topics under the consideration include: ophthalmic drug delivery of N-acetylcarnosine eye drops and challenging endeavors facing the pharmaceutical scientist; clinical and functional types of activity of the developed and patented N-acetylcarnosine lubricant eye drops designed as 1% N-acetylcarnosine prodrug of L-carnosine containing a mucoadhesive cellulose-based compound combined with corneal absorption promoters in a drug delivery system; management of age-related serious or disabling eye diseases in humans with N-acetylcarnosine eye drop therapeutic platform (age-related cataracts, ocular inflammation, age-related macular degeneration , macular dystrophies, ocular manifestations of diabetes , hypertonic retinopathy, primary open angle glaucoma, vitreous lesions) ; development and molecular mechanisms of ocular therapeutic activities of carnosine derivatives in the visual system. Through this article we can perceive some helpful recent patents according to the title of the issue. The biologically significant applications of carnosine mimetics including those in ophthalmology were patented by Dr. Babizhayev and the alliance Groups (WO 2004/028536 A1; WO 94/19325; WO 95/12581; WO 2004/064866 A1).

Topics: Administration, Topical; Antioxidants; Carnosine; Drug Delivery Systems; Eye Diseases; Humans; Ophthalmic Solutions; Patents as Topic