Models of Intraocular Pressure and Endothelin-1 Induced Optic Nerve Damage

Optic neuropathies are among the leading causes of blindness in Canada. Of these diseases, open-angle glaucoma is by far the most common affecting 1-2% of persons over the age of 40 years. It leads to visual disability and blindness by damaging retinal ganglion cells which are specialized neurons in retina which transmit signals to the brain via their axons which make up the optic nerve. The precise mechanism of how these messages are interrupted and how retinal ganglion cells actually die is unknown. To address this question, this research programme will use experimental models of optic neuropathy in rats. Our work to date has suggested that a class of supporting cells called astrocytes are intimately involved in retinal ganglion cell health by their interaction with their axons. Specifically we have shown that a specific receptor called endothelin B (ETB) is expressed more readily by astrocytes in damaged eyes. Using a variety of techniques we will determine the mechanism of ETB expression and its relation to retinal ganglion cell loss. We will also use a strain of knockout rats in whom ETB is not functional to determine the modulating role of ETB. The knowledge from this programme will lead to new therapeutic approaches targeted to ETB which will have a positive impact in the treatment of the optic neuropathies.