Nuclear atrophy of retinal ganglion cells precedes the bax-dependent stage of apoptosis.

Nickells Lab // Publications // Mar 11 2013

PubMed ID: 23422829

Author(s): Janssen KT, Mac Nair CE, Dietz JA, Schlamp CL, Nickells RW. Nuclear atrophy of retinal ganglion cells precedes the bax-dependent stage of apoptosis. Invest Ophthalmol Vis Sci. 2013 Mar 11;54(3):1805-15. doi: 10.1167/iovs.11-9310. PMID 23422829

Journal: Investigative Ophthalmology & Visual Science, Volume 54, Issue 3, Mar 2013

PURPOSE Retinal ganglion cells atrophy during the execution of the intrinsic apoptotic program. This process, which has been termed the apoptotic volume decrease (AVD) in other cell types, has not been well-characterized in ganglion cells.

METHODS Acute optic nerve crush was used to examine neuronal atrophy in the ganglion cell layer in wild-type and Bax-deficient mice. Nuclear size was measured from retinal wholemounts. Heterochromatin formation was assessed using transmission electron microscopy, whereas histone H4 acetylation was monitored using immunofluoresence. Ganglion cell and retinal transcript abundance was measured using quantitative PCR.

RESULTS Nuclear and soma sizes linearly correlated in both control and damaged retinas. Cells in wild-type mice exhibited nuclear atrophy within 1 day after optic nerve damage. Three days after crush, nuclear atrophy was restricted to ganglion cells identified by retrograde labeling, while amacrine cells also exhibited some atrophy by 5 days. Similar kinetics of nuclear atrophy were observed in cells deficient for the essential proapoptotic gene Bax. Bax-deficient cells also exhibited other nuclear changes common in wild-type cells, including the deacetylation of histones, formation of heterochromatin, and the silencing of ganglion cell-specific gene expression.

CONCLUSIONS Retinal ganglion cell somas and nuclei undergo the AVD in response to optic nerve damage. Atrophy is rapid and precedes the Bax-dependent committed step of the intrinsic apoptotic pathway.