Caspase inhibitors block the retinal ganglion cell death following optic nerve transection

Priya Chaudhary, F. Ahmed, P. Quebada, S. C. Sharma

Research output: Contribution to journalArticle

131 Citations (Scopus)

Abstract

Retinal ganglion cells die by apoptosis following axotomy. The molecular mechanisms of the retinal ganglion cell death are not well understood. In the present study using RT-PCR and in situ hybridization techniques we demonstrated that levels of mRNA for Bcl-2 and Bcl-x decreased after axotomy. Bax levels remained high until 4 days after axotomy, decreased by day 7 and remained low up to day 10. CPP32 levels increased at day 7 and remained high after optic nerve cut. We studied whether inhibitors of CPP32/caspase would save the axotomy induced ganglion cell death. DEVD-CHO (Ac-Asp-Glu-Val- aspartic acid aldehyde) and DEVD-FMK (Z-Asp-Glu-Val-Asp-FMK), caspase inhibitors, when administered intraocularly at the time of optic nerve cut, at days 3 and 7 protect about 30-35% the ganglion cells from death. We further demonstrated that the number of reactive microglia decrease in the retina when the inhibitors were given as compared with retina where no inhibitors were given. The present data offers new avenues for studying the complex interactions between the retinal ganglion cell death and the activation of resident microglia/macrophages.

Original languageEnglish (US)
Pages (from-to)36-45
Number of pages10
JournalMolecular Brain Research
Volume67
Issue number1
DOIs
StatePublished - Apr 6 1999
Externally publishedYes

Fingerprint

Optic Nerve Injuries
Axotomy
Caspase Inhibitors
Retinal Ganglion Cells
Cell Death
Microglia
Optic Nerve
Ganglia
Retina
Aspartic Acid
Aldehydes
In Situ Hybridization
Macrophages
Apoptosis
Polymerase Chain Reaction
Messenger RNA

Keywords

  • Apoptosis
  • Axotomy
  • Caspase inhibitor
  • Microglia
  • Retinal ganglion cell

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

Caspase inhibitors block the retinal ganglion cell death following optic nerve transection. / Chaudhary, Priya; Ahmed, F.; Quebada, P.; Sharma, S. C.

In: Molecular Brain Research, Vol. 67, No. 1, 06.04.1999, p. 36-45.

Research output: Contribution to journalArticle

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