Potential mechanisms of retinal ganglion cell type-specific vulnerability in glaucoma

Glaucoma is a neurodegenerative disease characterised by progressive damage to the reti-nal ganglion cells (RGCs), the output neurons of the retina. RGCs are a heterogenous classof retinal neurons which can be classified into multiple types based on morphological, func-tional and genetic characteristics. This review examines the body of evidence supportingtype-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. Severalmechanisms may contribute to type-specific vulnerability, including differences in theexpression of calcium-permeable receptors (for example pannexin-1, P2X7, AMPA and tran-sient receptor potential vanilloid receptors), the relative proximity of RGCs and their den-drites to blood supply in the inner plexiform layer, as well as differing metabolicrequirements 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 like lyreveal a rich area of investigation for potential treatment targets.