title: BAX to basics: How the BCL2 gene family controls the death of retinal ganglion cells.
abstract: Retinal ganglion cell (RGC) death is the principal consequence of injury to the optic nerve. For several decades, we have understood that the RGC death process was executed by apoptosis, suggesting that there may be ways to therapeutically intervene in this cell death program and provide a more direct treatment to the cells and tissues affected in diseases like glaucoma. A major part of this endeavor has been to elucidate the molecular biological pathways active in RGCs from the point of axonal injury to the point of irreversible cell death. A major component of this process is the complex interaction of members of the BCL2 gene family. Three distinct family members of proteins orchestrate the most critical junction in the apoptotic program of RGCs, culminating in the activation of pro-apoptotic BAX. Once active, BAX causes irreparable damage to mitochondria, while precipitating downstream events that finish off a dying ganglion cell. This review is divided into two major parts. First, we summarize the extent of knowledge of how BCL2 gene family proteins interact to facilitate the activation and function of BAX. This area of investigation has rapidly changed over the last few years and has yielded a dramatically different mechanistic understanding of how the intrinsic apoptotic program is run in mammalian cells. Second, we provided a comprehensive analysis of nearly two decades of investigation of the role of BAX in the process of RGC death, much of which has provided many important insights into the overall pathophysiology of diseases like glaucoma.
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Maes
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Cassandra L
authors.initials: CL
authors.lastname: Schlamp
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, WI, USA. Electronic address: nickells@wisc.edu.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Nickells
mesh_terms: D000818:Animals; D017209:Apoptosis; D016923:Cell Death; D005901:Glaucoma; D006801:Humans; D009900:Optic Nerve / Q000378:metabolism / Q000473:pathology*; D009901:Optic Nerve Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D051028:bcl-2-Associated X Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: C000595707:BCL2 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein
keywords: BAX; BCL2 gene family; BH3-only proteins; Glaucoma; Intrinsic and extrinsic apoptosis; Mitochondrial outer membrane; Neuroinflammation; Retinal ganglion cells; Secondary degeneration