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VT PHAK EYE DROPS THE CRYSTALLINE LENS AND SENILE CATARACTS What is the lens? (1) The crystalline lens is located just behind the iris. It is a transparent, biconvex structure that refracts light and focuses it on the retina. The lens can be divided into several areas, from the surface to the center: The capsule, a structure of exchange between the lens and the aqueous and vitreous humour. The epithelium, a layer of cuboidal cells present within the anterior capsule only. It is the single regenerating tissue in the lens; throughout life, epithelial cells divide, move to the equator, elongate, loose their nucleus and become new lens fibers. The lens fibers are the bulk of the lens, divided into the cortex and the nucleus: - The Cortex is composed of recent lens fibers. The cytoplasm of the lens fiber cells contains crystallines, a class of water-soluble proteins. - The Nucleus, the innermost part of the lens, contains the old lens fibers which have lost all major organelles. All lens fibers produced during the life of the animal are packed in the nucleus and divided in thin concentric layers along time. The lens is maintained by thin but very strong suspensory ligaments, the zonules of Zinn, attached one end to the lens capsule and on the other end to the ciliary processes of the ciliary body. The lens is an avascular structure that depends integrally on the aqueous and vitreous humours for nutrition. The lens capsule and the epithelium regulate most of the exchanges between the aqueous humour and crystalline cells. The lens serves a dual function: 1. The lens makes adjustments for close or distance vision, by changes in its curvature. This process is called accommodation. The lens gradually gets firmer with age, diminishing the ability to accommodate. 2. The lens protects the retina by absorbing ultra-violets. VT PHAK EYE DROPS The role of Glutathione in the lens (4) Glutathione is a tri-peptide made of the amino acids glutamate, cysteine, and glycine and is also called glutamylcysteinylglycine or GSH. Glutathione exerts essential physiological functions aimed at preserving lens transparency: Prevention of oxidative cell damage Throughout life, the lens is exposed to ultra-violets radiations that induce free radicals production. These free radicals are continuously inactivated by antioxidant systems. Glutathione is the most important antioxidant system of the lens. Amino acid transport The lens is rich in proteins (35%). 85% of these proteins are water-soluble. They are called crystallines and are responsible for lens transparency. The components used to produce these crystallines come from the aqueous humour. These components are amino-acids and their transfer to the lens requires a polypeptide found on lens epithelium, glutathione. Protein synthesis and enzyme activation Crystallines production requires glutathione as an enzyme activator and a source of amino-acids. CRYSTALLINE LENS AQUEOUS HUMOUR VITREOUS HUMOUR PROTEIN SYNTHESIS NEW CRYSTALLINES UV GLUTATHIONE Glutathione Amino-acids Free radicals Free radicals destruction The role of Glutathione in the maintenance of lens transparency VT PHAK EYE DROPS The Crystalline lens maturation process (senile cataract) & glutathione role (2, 5) Glutathione availability decreases with age, leading to free-radicals accumulation and a decrease in protein synthesis. Thus, crystallines are not regenerated and free-radicals induce crystallines aggregation and opacification leading to a loss in lens transparency. Senile cataract is occurring. CRYSTALLINE LENS AQUEOUS HUMOUR VITREOUS HUMOUR PROTEIN SYNTHESIS NEW CRYSTALLINES UV GLUTATHIONE AGGREGATION + OPACIFIACTION OF CRYSTALLINES Glutathione Amino-acids Free radicals Free radicals destruction The degenerating process occuring in the old crystalline lens Advanced cataracts are a leading cause of blindness in dogs and are generally recognised by pet owners either through the cloudy, whitish-blue appearance of the eye, or by the resulting decrease in the dog's vision. VT PHAK EYE DROPS VT PHAK EYE DROPS INGREDIENTS AIM AT SLOWING DOWN SENILE CATARACT EVOLUTION INGREDIENTS CYTOCHROM C GLYCINE VITAMINE PP (NICOTINAMIDE) BORIC ACID AND ITS SODIUM SALT PROPERTIES BENEFITS • Reduces damages induced by • Free radical scavenger free radicals (aggregation and opacification of crystallines) • Antioxidant • Amino-acid part of Glutathione • Glutathione regeneration (6) • Opacification slow down composition • Glutathione regeneration • Regenerates the reduced Glutathione pool (7) • Opacification slow down • Antimicrobial agent • Microbiological growth reduction Cytochrome C metabolites protect lens cells from the oxidative stress induced by free radicals. (3, 8) CRYSTALLINE LENS AQUEOUS HUMOUR VITREOUS HUMOUR P ROTEIN SYNTHESIS GLYCINE N EW CRYSTALLINES UV CYTOCHROME C Glutathione Amino-acids GLUTATHIONE Free radicals Glycine Mode of action of VT Phak ingredients in the lens VITAMINE PP Free radicals destruction VT PHAK EYE DROPS CONDITIONS FOR USE VT Phak eye drops can be used in the early stages of senile lens opacification. DIRECTIONS FOR USE: Instil 1 drop per eye twice daily for 20 days a month. For increased efficacy, VT Phak eye drops can be associated with VT Phak Syrup. 1. 2. 3. 4. 5. 6. 7. 8. CLERC B, (1997). Cristallin. In : Ophtalmologie Vétérinaire, 2ème Edition, Editions du Point Vétérinaire, 375-410. JAIN NK, RAWAL UM, (1999). Influence of UV-irradiation on enzymes in mouse ocular lens: in vitro studies. Indian J Ophthalmol, 47, 25-29. MA W, WANG RR, KLEIMAN NJ, (1997). Microperoxidases catalytically degrade reactive oxygen species and may be anti-cataract agents.Spector A. Exp Eye Res., 65, 4, 457-470. PARRIS M. KIDD. Glutathione: Systemic Protectant Against Oxidative and Free Radical Damage http://www.thorne.com/altmedrev/fulltext/glut.html ROSELEN G, (2005). Le vieillissement de l’oeil chez l’animal. Bull. Acad. Vet. France, 158, 3, 195-211. TESHIGAWARA M, MATSUMOTO S, TSUBOI S, OHMORI S, (1995). Changes in levels of glutathione and related compounds and activities of glutathione-related enzymes during rat liver regeneration. Res Exp Med (Berl), 195, 2, 55-60. VOGEL R, WIESINGER H, HAMPRECHT B, DRINGEN R, (1999). The regeneration of reduced glutathione in rat forebrain mitochondria identifies metabolic pathways providing the NADPH required. Neurosci Lett., 12, 275, 2, 97-100. ZHOU W, MA W, CHIGNELL CF, RESZKA KJ, (2000). Investigation of the mechanism of action of microperoxidase-11, (MP11), a potential anti-cataract agent, with hydrogen peroxide and ascorbate.Spector A. Exp Eye Res., 71, 2, 183-194.