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Bax Contributes to Retinal Ganglion Cell Dendritic Degeneration During Glaucoma.
Authors Risner ML, Pasini S, McGrady NR, Calkins DJ
Submitted By Submitted Externally on 1/10/2022
Status Published
Journal Molecular neurobiology
Year 2022
Date Published 1/1/2022
Volume : Pages Not Specified : Not Specified
PubMed Reference 34984584
Abstract The BCL-2 (B-cell lymphoma-2) family of proteins contributes to
mitochondrial-based apoptosis in models of neurodegeneration, including
glaucomatous optic neuropathy (glaucoma), which degrades the retinal ganglion
cell (RGC) axonal projection to the visual brain. Glaucoma is commonly
associated with increased sensitivity to intraocular pressure (IOP) and involves
a proximal program that leads to RGC dendritic pruning and a distal program that
underlies axonopathy in the optic projection. While genetic deletion of the
Bcl2-associated X protein (Bax-/-) prolongs RGC body survival in models of
glaucoma and optic nerve trauma, axonopathy persists, thus raising the question
of whether dendrites and the RGC light response are protected. Here, we used an
inducible model of glaucoma in Bax-/- mice to determine if Bax contributes to
RGC dendritic degeneration. We performed whole-cell recordings and dye filling
in RGCs signaling light onset (aON-Sustained) and offset (aOFF-Sustained). We
recovered RGC dendritic morphologies by confocal microscopy and analyzed
dendritic arbor complexity and size. Additionally, we assessed RGC axon function
by measuring anterograde axon transport of cholera toxin subunit B to the
superior colliculus and behavioral spatial frequency threshold (i.e., spatial
acuity). We found 1 month of IOP elevation did not cause significant RGC death
in either WT or Bax-/- retinas. However, IOP elevation reduced dendritic arbor
complexity of WT aON-Sustained and aOFF-Sustained RGCs. In the absence of Bax,
aON- and aOFF-Sustained RGC dendritic arbors remained intact following IOP
elevation. In addition to dendrites, neuroprotection by Bax-/- generalized to
aON-and aOFF-Sustained RGC light- and current-evoked responses. Both anterograde
axon transport and spatial acuity declined during IOP elevation in WT and Bax-/-
mice. Collectively, our results indicate Bax contributes to RGC dendritic
degeneration and distinguishes the proximal and distal neurodegenerative
programs involved during the progression of glaucoma.


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