BCLX_L gene therapy moderates neuropathology in the DBA/2J mouse model of inherited glaucoma.

ABSTRACT: Axonal degeneration of retinal ganglion cells (RGCs) causes blindness in glaucoma. Currently, there are no therapies that target axons to prevent them from degenerating. Activation of the BAX protein has been shown to be the determining step in the intrinsic apoptotic pathway that causes RGCs to die in glaucoma. A putative role for BAX in axonal degeneration is less well elucidated. BCLX_L (BCL2L1) is the primary antagonist of BAX in RGCs. We developed a mCherry-BCLX_L fusion protein, which prevented BAX recruitment and activation to the mitochondria in tissue culture cells exposed to staurosporine. This fusion protein was then packaged into adeno-associated virus serotype 2, which was used to transduce RGCs after intravitreal injection and force its overexpression. Tra

SUBMITTER: Donahue RJ 

PROVIDER: S-EPMC8355227 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature