Activation of caspase-3 in the retina of transgenic rats with the rhodopsin mutation S334ter during photoreceptor degeneration

Changdong Liu, Yiwen Li, Min Peng, Alan M. Laties, Rong Wen

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Abstract

The role of caspase-3 in photoreceptor degeneration was examined in a line of transgenic rats that carry a rhodopsin mutation S334ter. Photoreceptor degeneration in these animals is rapid. It is detected as early as postnatal day (PD) 8, and by PD 20, only one of the original 12 rows of nuclei remain in the outer nuclear layer. At PD 11 and 12, the number of photoreceptors dying per day reaches a peak of ~30% of the total photoreceptors in the retina. Coincident with this rapid degeneration is an increase in caspase-3-like activity as assessed by the cleavage of a fluorescent substrate N-acetyl-Asp-Glu-Val-Asp-aminomethylcoumarin and an increase in activated caspase-3 as determined by Western blot analysis for its 12 kDa subunit. Intraocular injection of an irreversible caspase-3 inhibitor N-benzyloxycarbonal-Asp(OMe)-Glu(OMe)-Val-Asp(Ome)- fluoromethyketone partially protected photoreceptors from degeneration. These findings indicate that a caspase-3-dependent mechanism is operative in photoreceptor death in the transgenic rats under investigation.

Original languageEnglish (US)
Pages (from-to)4778-4785
Number of pages8
JournalJournal of Neuroscience
Volume19
Issue number12
StatePublished - Jun 15 1999
Externally publishedYes

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Keywords

  • Caspase-3
  • Degeneration
  • Photoreceptors
  • Retina
  • Rhodopsin mutation
  • Transgenic rat
  • Z-DEVD-fmk

ASJC Scopus subject areas

  • Neuroscience(all)

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