Lipid Peroxidation and Cataracts

Abstract

Cataract formation represents a serious problem in the elderly, with approximately 25% of the population aged >65 years and about 50% aged >80 years experiencing a serious loss of vision as a result of this condition. Not only do cataracts diminish quality of life, they also impose a severe strain on global healthcare budgets. In the US, 43% of all visits to ophthalmologists by Medicare patients are associated with cataract. Surgery represents the standard treatment of this condition, and 1.35 million cataract operations are performed annually in the US, costing 3.5 billion US dollars (year of costing, 1998). Unfortunately, the costs of surgical treatment and the fact that the number of patients exceeds surgical capacities result in many patients being blinded by cataracts worldwide. This situation is particularly serious in developing countries; worldwide 17 million people are blind because of cataract formation, and the problem will grow in parallel with aging of the population. In any event, surgical removal of cataracts may not represent the optimal solution. Although generally recognised as being one of the safest operations, there is a significant complication rate associated with this surgical procedure. Opacification of the posterior lens capsule occurs in 30-50% of patients within 2 years of cataract removal and requires laser treatment, a further 0.8% experience retinal detachments, approximately 1% are rehospitalised for corneal problems, and about 0.1% develop endophthalmitis. Although the risks are small, the large number of procedures performed means that 26,000 individuals develop serious complications as a result of cataract surgery annually in the US alone. Thus, risk and cost factors drive the investigation of pharmaceutical approaches to the maintenance of lens transparency. The role of free radical-induced lipid oxidation in the development of cataracts has been identified. Initial stages of cataract are characterised by the accumulation of primary (diene conjugates, cetodienes) lipid peroxidation (LPO) products, while in later stages there is a prevalence of LPO fluorescent end-products. A reliable increase in oxiproducts of fatty acyl content of lenticular lipids was shown by a direct gas chromatography technique producing fatty acid fluorine-substituted derivatives. The lens opacity degree correlates with the level of the LPO fluorescent end-product accumulation in its tissue, accompanied by sulfhydryl group oxidation of lens proteins due to a decrease of reduced glutathione concentration in the lens. The injection of LPO products into the vitreous has been shown to induce cataract. It is concluded that peroxide damage of the lens fibre membranes may be the initial cause of cataract development. N-acetylcarnosine (as the ophthalmic drug Can-C), has been found to be suitable for the nonsurgical prevention and treatment of age-related cataracts. This molecule protects the crystalline lens from oxidative stress-induced damage, and in a recent clinical trial it was shown to produce an effective...

Current Ocular Drug Delivery Challenges for N-acetylcarnosine: Novel Patented Routes and Modes of Delivery, Design for Enhancement of Therapeutic Activity and Drug Delivery Relationships

“…In many cases prodrugs may offer a way to overcome the poor drug-like properties of a very potent lead and provide the opportunity to convert a non-developable natural molecule subjected to enzymatic hydrolysis into a potent patented candidate for clinical use. Natural histidinecontaining dipeptide L-Carnosine ( -alanyl-L-histidine) and its ophthalmic prodrug bioactivating N-acetylcarnosine (Nacetyl--alanyl-L-histidine) are part of this group of products [160][161][162][163][164][165][166][167][168][169][170][171][172][173][174][175][176][177]. N-acetylcarnosine (NAC), like its parent compound, L-carnosine, occurs naturally throughout the human body .…”

“…Thus, in order to change an antioxidant status, tissue enzymes can modify the NAC prodrug molecule and deacetylation will increase in vivo the resistance of lens tissues and its cells to oxidative stress. The topical administration of N-acetylcarnosine as a universal bioactivating antioxidant for vision in the developed and patented lubricant eye drop formulations delivers pure L-carnosine and allows its increased intraocular absorption into the aqueous humor surrounding the lens, thus enabling significant improvements in anti-cataract drug efficacy and the minimization of side-effect from either local or systemic drug absorption/bioavailability to the eye, and also creates optimization effects in the number of ocular degenerative age-dependent disorders [161,162,177 ]. (3b).…”

“…The R&D team at Innovative Vision Products, Inc. (IVP, County of New Castle, Delaware, USA) studied the effects of 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 [162,179]. Several references [185][186][187][188][189][190] appear to raise a prima facie case of obviousness against the claimed method for prevention or treatment of an eye disease [185][186][187][188][189][190].…”

Antioxidant Properties of Indole-3-Acetic Acid based Biopolymeric Hydrogels

“…The formation and identification of biocomposite hydrogel confirmed by FT-IR, 1 H NMR and 13 C NMR, respectively. The hydrogels have exhibited a maximum of swelling at acidic pH, while the swelling ratio decreases with increase alkalinity.…”

“…Based on literature survey already reported alphatic hydrogels but the present study is focused on the synthesis of indole-3-acetic acid (aromatic heterocyclic hydrogel) based biocomposite hydrogels. The structural characterization, thermal studies and morphological analysis of biocomposite hydrogels deliberated by various instrumentation technique like Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy ( 1 H NMR, 13 C NMR) and TGA-DTA. Swelling equilibrium in various pH solutions in the range of 3-10.…”