Mechanism of retinal ganglion cells death in secondary degeneration of the optic nerve

Hani Levkovitch-Verbin, Rima Dardik, Shelly Vander, Shlomo Melamed

Research output: Contribution to journalArticlepeer-review

Abstract

In central nervous system injury, the secondary degeneration process is known to play a major role in determining the final extent of impairment. Here, we investigated the mechanism of retinal ganglion cell (RGC) death in secondary degeneration of the optic nerve using a unique model that allows morphological separation between primary and secondary degeneration. A partial transection model was applied unilaterally in 110 Wistar rat eyes. The rate of apoptosis was evaluated in primary and secondary degeneration over a period of 6 months using the Hoechst staining technique. The involvement of caspase 3 and members of the Bcl-2 family (Bax, Bad, Bcl-2 and Bcl-xl) was evaluated at multiple time points for 6 months after the injury by immunohistochemistry and RT-PCR. We found that in secondary degeneration of the optic nerve, RGCs died by apoptosis from day 3-6 months following the injury, peaking at 3 months (16.3% ± 2.5% apoptotic cells, p < 0.01). Both primary and secondary degeneration of the optic nerve resulted in caspase 3 activation, which was longer and more intense in the former. Similarly, both primary and secondary degeneration led to significant (p < 0.05) downregulation of the pro-survival genes Bcl-2 and Bcl-x-L and up-regulation of the pro-apoptotic genes Bax and Bad (p < 0.05), with a suggested delay in secondary degeneration. Thus, secondary degeneration of the optic nerve leads to RGC apoptosis over long periods in a similar mechanism as in primary degeneration.

Original languageEnglish
Pages (from-to)127-134
Number of pages8
JournalExperimental Eye Research
Volume91
Issue number2
DOIs
StatePublished - Aug 2010

Keywords

  • Apoptosis
  • Bcl-2
  • Glaucoma
  • Optic nerve
  • Secondary degeneration

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