Apoptotic photoreceptor cell death in mouse models of retinitis pigmentosa

Proc Natl Acad Sci U S A. 1994 Feb 1;91(3):974-8. doi: 10.1073/pnas.91.3.974.


Retinitis pigmentosa (RP) is a group of inherited human diseases in which photoreceptor degeneration leads to visual loss and eventually to blindness. Although mutations in the rhodopsin, peripherin, and cGMP phosphodiesterase genes have been identified in some forms of RP, it remains to be determined whether these mutations lead to photoreceptor cell death through necrotic or apoptotic mechanisms. In this paper, we report a test of the hypothesis that photoreceptor cell death occurs by an apoptotic mechanism in three mouse models of RP: retinal degeneration slow (rds) caused by a peripherin mutation, retinal degeneration (rd) caused by a defect in cGMP phosphodiesterase, and transgenic mice carrying a rhodopsin Q344ter mutation responsible for autosomal dominant RP. Two complementary techniques were used to detect apoptosis-specific internucleosomal DNA fragmentation: agarose gel electrophoresis and in situ labeling of apoptotic cells by terminal dUTP nick end labeling. Both methods showed extensive apoptosis of photoreceptors in all three mouse models of retinal degeneration. We also show that apoptotic death occurs in the retina during normal development, suggesting that different mechanisms can cause photoreceptor death by activating an intrinsic death program in these cells. These findings raise the possibility that retinal degenerations may be slowed by interfering with the apoptotic mechanism itself.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3',5'-Cyclic-GMP Phosphodiesterases / genetics
  • Animals
  • Apoptosis / genetics*
  • Disease Models, Animal
  • Humans
  • Intermediate Filament Proteins / genetics
  • Membrane Glycoproteins*
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Nerve Tissue Proteins*
  • Peripherins
  • Photoreceptor Cells / pathology*
  • Retina / growth & development
  • Retina / pathology
  • Retinal Degeneration / genetics
  • Retinal Degeneration / pathology
  • Retinitis Pigmentosa / genetics*
  • Retinitis Pigmentosa / pathology*
  • Rhodopsin / genetics


  • Intermediate Filament Proteins
  • Membrane Glycoproteins
  • Nerve Tissue Proteins
  • PRPH protein, human
  • PRPH2 protein, human
  • Peripherins
  • Prph2 protein, mouse
  • Rhodopsin
  • 3',5'-Cyclic-GMP Phosphodiesterases