AN OCULAR NEUROTROPHIC FACTOR TO TREAT GLAUCOMA

THE CILIARY GANGLION INNERVATES SEVERAL IMPORTANT EYE TISSUES, INCLUDING THE CILIARY MUSCLE AND BODY, AND HAS BEEN SHOWN TO REGULATE AQUEOUS OUTFLOW AND ACCOMMODATION. THE EYE DISORDERS, GLAUCOMA AND PRESBYOPIA, MAY INVOLVE THE CILIARY GANGLION THROUGH ITS REGULATION OF AQUEOUS OUTFLOW AND VISUAL ACCOMMODATION. A SUBSTANCE THAT COULD DIRECTLY AND SPECIFICALLY STIMULATE THE CILIARY GANGLION MAY BE AN EFFECTIVE MEANS OF TREATING THESE DISORDERS. A NEUROTROPHIC FACTOR (NTF) HAS BEEN PURIFIED FROM PIG LUNG THAT SHOULD BE USEFUL IN TREATING GLAUCOMA AND PRESBYOPIA. THE MOLECULAR WEIGHT, MAMMALIAN TISSUE SOURCE, NEURONAL SPECIFICITY, AND AMINO ACID COMPOSITION INDICATE THAT IT IS DIFFERENT FROM PREVIOUSLY REPORTED NEUROTROPHIC FACTORS. THE AIMS OF THIS PROJECT ARE TO SEQUENCE THIS PROTEIN AND TORAISE POLYCLONAL ANTIBODIES AGAINST A SYNTHETIC AMINO ACID SEQUENCE OR NATIVE MOLECULE. THESE ANTIBODIES WILL BE USED TO MAKE AN IMMUNOAFFINITY COLUMN THAT WILL BE UTILIZED IN PURIFYING LARGE QUANTITIES OF THIS FACTOR. THE LONG-TERM GOAL WILL BE TO TEST THIS NTF IN ANIMAL MODELS OF GLAUCOMA AND PRESBYOPIA. THE NTF MAY ACT IN THE TREATMENT OF GLAUCOMA AND PRESBYOPIA BY STIMULATING CILIARY GANGLION NEURONS TO MAKE CHOLINE ACETYLTRANSFERASE, THE ENZYME THAT CATALYZES THE FORMATION OF ACETYLCHOLINE; BY INCREASING THE NUMBER OF AXONS INNERVATING THE CILIARY MUSCLE; AND BY POSSIBLY INCREASING THE NUMBER OF POSTJUNCTIONAL ACETYLCHOLINE RECEPTORS, ALL OF WHICH MAY DECREASE INTRAOCULAR PRESSURE. BY ANALOGY WITH THE PROPERTIES OF NERVE GROWTH FACTOR, THE NTF'S EFFECTS WOULD BE RELATIVELY SLOW ACTING, BUT LONG LASTING, AND COULD BE AN ALTERNATIVE TO PRESENTLY AVAILABLE DRUGS USED TO TREAT GLAUCOMA, WHICH NEED TO BE ADMINISTERED FREQUENTLY.