1. Field of the Invention
The present invention relates to a method of preventing retinal ganglion cell death, associated with glaucoma, by administering to retinal ganglion cells of a mammal, a compound which blocks the putative non-inactivating sodium ion channels of the above cell type.
2. Brief Description of the Art
Glaucoma is an optic neuropathy associated with elevated intraocular pressures which are too high for normal function of the eye, and results in irreversible loss of visual function. (See for example, Dreyer et al "Elevated glutamate levels in the vitreous body of human and monkeys with glaucoma", Arch. Ophthalmology 114:299-305, 1996) It is estimated in medical science that glaucoma afflicts approximately 2 per cent of the population over the age of forty years, and is therefore a serious health problem. Ocular hypertension, i.e. the condition of elevated intraocular pressure, which has not yet caused irreversible damage, is believed to represent the earliest phase of glaucoma. Many therapeutic agents have been devised and discovered in the prior art for the treatment or amelioration of glaucoma and of the condition of increased intraocular pressure which precedes glaucoma.
Primary open angle glaucoma (POAG) is associated with a rise in intraocular pressure (IOP). This increase in IOP is believed to contribute to the loss of optic nerve function which ultimately leads to blindness. Reduction of IOP is therefore a crucial component in the management of POAG. However, in many individuals lowering of IOP is not sufficient or ineffective in preventing vision loss associated with POAG.
It is thought that a novel class of sodium channels residing within the optic nerve of the rat are responsible for damage to the rat optic nerve following anoxia or hypoxia. However, in glaucoma the sequence of pathological events leading to the loss of optic nerve function, is not known.
The drugs currently utilized in the treatment of glaucoma include miotics (e.g., pilocarpine, carbachol, and acetylcholinesterase inhibitors), sympathomimetrics (e.g., epinephrine and dipivalylepinephrine), beta-blockers (e.g., betaxolol, levobunolol and timolol), alpha-2 agonists (e.g., para-amino clonidine) and carbonic anhydrase inhibitors (e.g., acetazolamide, methazolamide and ethoxzolamide). Miotics and sympathomimetics are believed to lower intraocular pressure by increasing the outflow of aqueous humor, while beta-blockers, alpha-2 agonists and carbonic anhydrase inhibitors are believed to lower intraocular pressure by decreasing the formation of aqueous humor. All five types of drugs have potential side effects. Miotics, such as pilocarpine, can cause blurring of vision and other visual side effects which may either decrease patient compliance or require termination of miotic drug therapy. Carbonic anhydrase inhibitors can also cause serious side effects which affect patient compliance and/or necessitate withdrawal of the drug therapy. At least one beta-blocker, timolol, has increasingly become associated with serious pulmonary side effects attributable to its effect on beta-2 receptors in pulmonary tissue.
As a result additional antiglaucoma drugs are being developed, e.g., prostaglandin derivatives, muscarinic antagonists, etc. However, none of the above drugs are designed to directly interact with the retinal ganglion cell and its associated axon.
Thus, it would be desirable to prevent the loss of ganglion cell body and axon function, which may be associated with glaucoma by a biological mechanism which does not modulate aqueous humor dynamics and therefore intraocular pressure. Moreover, it would be desirable to treat the retinal ganglion cell body and axon of a mammal directly to prevent the destruction thereof by the glaucomatous condition.