Drugs 2007; 67 (5): 725-759 REVIEW ARTICLE 0012-6667/07/0005-0725/$49.95/0 © 2007 Adis Data Information BV. All rights reserved. Pharmacological Neuroprotection for Glaucoma Glyn Chidlow, 1,2 John P.M. Wood 1,2 and Robert J. Casson 1,2 1 Ophthalmic Research Laboratories, South Australian Institute of Ophthalmology, Hanson Institute, Adelaide, South Australia, Australia 2 University of Adelaide, Adelaide, South Australia, Australia Contents Abstract .................................................................................... 726 1. Epidemiology and Definitions ............................................................. 726 2. Outline of Relevant Pathology ............................................................. 728 3. Pathogenesis of Glaucoma ............................................................... 728 3.1 The Mechanical Theory ............................................................... 728 3.2 The Vascular Hypothesis .............................................................. 729 3.3 Autoimmunity and Heat Shock Proteins ................................................ 731 4. Laboratory Models of Glaucoma .......................................................... 731 5. Criteria for Evaluating Neuroprotection ..................................................... 732 6. Targets for Neuroprotection ............................................................... 733 6.1 Glutamate Receptors ................................................................ 733 6.1.1 Is There Evidence for Increased Glutamate in Glaucoma? ......................... 733 6.1.2 NMDA Receptor Antagonists .................................................... 734 6.1.3 How are NMDA Receptor Antagonists Neuroprotective in Experimental Glaucoma? 735 6.1.4 Summary ...................................................................... 735 6.2 Boosting Protective Autoimmunity ..................................................... 735 6.2.1 Glatiramer Acetate ............................................................ 736 6.2.2 Summary ...................................................................... 736 6.3 Neurotrophin Deprivation ............................................................. 736 6.3.1 Obstructed Axonal Transport .................................................... 737 6.3.2 Neurotrophin Deprivation ....................................................... 737 6.3.3 Brain-Derived Neurotrophic Factor ............................................... 737 6.3.4 Other Neurotrophic Factors ..................................................... 737 6.3.5 Summary ...................................................................... 738 6.4 Nitric Oxide Synthesis ................................................................. 738 6.4.1 Aminoguanidine ............................................................... 738 6.4.2 Summary ...................................................................... 739 6.5 Voltage-Gated Sodium Channels ..................................................... 739 6.5.1 Phenytoin ..................................................................... 739 6.5.2 Summary ...................................................................... 740 6.6 Voltage-Gated Calcium Channels .................................................... 740 6.7 Oxidative Stress ...................................................................... 740 6.7.1 α-Tocopherol .................................................................. 741 6.7.2 Ginkgo biloba ................................................................. 741 6.7.3 Other Free Radical Scavengers .................................................. 742 6.7.4 Summary ...................................................................... 742 6.8 Heat Shock Proteins .................................................................. 742 6.8.1 Geranylgeranylacetone ........................................................ 743 6.8.2 Summary ...................................................................... 743 6.9 Retinal Ganglion Cell Death and Apoptosis ............................................ 743 6.9.1 Evidence for Apoptosis in Glaucoma ............................................ 743