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Abstract
Glaucoma is a neurodegenerative disease characterised by progressive damage to the retinal ganglion cells (RGCs), the output neurons of the retina. RGCs are a heterogenous class of retinal neurons which can be classified into multiple types based on morphological, functional and genetic characteristics. This review examines the body of evidence supporting type‐specific vulnerability of RGCs in glaucoma and explores potential mechanisms by which this might come about. Studies of donor tissue from glaucoma patients have generally noted greater vulnerability of larger RGC types. Models of glaucoma induced in primates, cats and mice also show selective effects on RGC types – particularly OFF RGCs. Several mechanisms may contribute to type‐specific vulnerability, including differences in the expression of calcium‐permeable receptors (for example pannexin‐1, P2X7, AMPA and transient receptor potential vanilloid receptors), the relative proximity of RGCs and their dendrites to blood supply in the inner plexiform layer, as well as differing metabolic requirements of RGC types. Such differences may make certain RGCs more sensitive to intraocular pressure elevation and its associated biomechanical and vascular stress. A greater understanding of selective RGC vulnerability and its underlying causes will likely reveal a rich area of investigation for potential treatment targets.
ACKNOWLEDGEMENTS
We would like to thank Ms Lidia Trogrlic and Mr Gene Venables for invaluable technical support with this project. This work was funded by the National Health and Medical Research Council of Australia project grants APP1138253 (ELF/KAV) and APP1061418 (ELF/AIJ). BVB is supported by an Australian Research Council future fellowship (130100338). We would also like to acknowledge the use of animals for generation of some of the figures. All experiments and handling of animals were conducted in compliance with the standards of the Association of Vision Research and Ophthalmology (ARVO) Statement for the Use of Animals in Ophthalmic and Vision Research as well as the institutional guidelines of The University of Melbourne Animal Ethics Committee (AEC) (Ethics ID 1614030).