Neuroprotection in glaucoma: recent and future directions.
OBJECTIVE
The concept of neuroprotective therapy for glaucoma is that damage to retinal ganglion cells (RGCs) may be prevented by intervening in neuronal death pathways. This review focuses on strategies for neuroprotection and summarizes preclinical studies that have investigated potential agents over the last 2 years.


RESULTS
Part of the challenge of studies in neuroprotection has been the utilization of an animal model that resembles human glaucoma. Several models have been utilized including acute and chronic intraocular pressure elevation, the DBA/2J mouse, optic nerve axotomy and crush. NMDA inhibitors continued to be explored however with limited success in human trials. Memantine failed to demonstrate neuroprotection in phase III clinical trials. Although its mechanism of neuroprotection has not been fully elaborated, topical brimonidine has shown some neuroprotective benefits. Exogeneous neurotrophins delay, but do not prevent, RGC death. Bioenergetic neuroprotection that is enhancing the energy supply to RGC has been explored with benefits in animal models. Other strategies include TNF-α, modulation of the immune system and inflammation, and blocking apoptotic signals and stem cells.


CONCLUSIONS
Animal models of glaucoma and neuroprotective strategies continue to be refined. Establishing consensus guidelines for the execution and design of translational research in neuroprotection may optimize the facilitation of neuroprotection research.
Department of Ophthalmology, University of Auckland, Auckland, New Zealand. h.daneshmeyer@auckland.ac.nz
Helen V
HV
Danesh-Meyer
D000818:Animals; D035843:Biomedical Research / Q000639:trends; D002470:Cell Survival; D004195:Disease Models, Animal; D005901:Glaucoma / Q000188:drug therapy*; D006801:Humans; D007429:Intraocular Pressure; D051379:Mice; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009901:Optic Nerve Diseases / Q000188:drug therapy*; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000502:physiology
D018696:Neuroprotective Agents