The role of mislocalized phototransduction in photoreceptor cell death of retinitis pigmentosa

Takeshi Nakao, Motokazu Tsujikawa, Shoji Notomi, Yasuhiro Ikeda, Kohji Nishida

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Most of inherited retinal diseases such as retinitis pigmentosa (RP) cause photoreceptor cell death resulting in blindness. RP is a large family of diseases in which the photoreceptor cell death can be caused by a number of pathways. Among them, light exposure has been reported to induce photoreceptor cell death. However, the detailed mechanism by which photoreceptor cell death is caused by light exposure is unclear. In this study, we have shown that even a mild light exposure can induce ectopic phototransduction and result in the acceleration of rod photoreceptor cell death in some vertebrate models. In ovl, a zebrafish model of outer segment deficiency, photoreceptor cell death is associated with light exposure. The ovl larvae show ectopic accumulation of rhodopsin and knockdown of ectopic rhodopsin and transducin rescue rod photoreceptor cell death. However, knockdown of phosphodiesterase, the enzyme that mediates the next step of phototransduction, does not. So, ectopic phototransduction activated by light exposure, which leads to rod photoreceptor cell death, is through the action of transducin. Furthermore, we have demonstrated that forced activation of adenylyl cyclase in the inner segment leads to rod photoreceptor cell death. For further confirmation, we have also generated a transgenic fish which possesses a human rhodopsin mutation, Q344X. This fish and rd10 model mice show photoreceptor cell death caused by adenylyl cyclase. In short, our study indicates that in some RP, adenylyl cyclase is involved in photoreceptor cell death pathway; its inhibition is potentially a logical approach for a novel RP therapy.

Original languageEnglish
Article numbere32472
JournalPloS one
Volume7
Issue number4
DOIs
Publication statusPublished - Apr 2 2012

Fingerprint

Light Signal Transduction
phototransduction
Photoreceptor Cells
Retinitis Pigmentosa
Cell death
photoreceptors
cell death
Cell Death
rods (retina)
Retinal Rod Photoreceptor Cells
rhodopsin
adenylate cyclase
Rhodopsin
Light
Adenylyl Cyclases
Transducin
Fish
Fishes
retinal diseases
Retinal Diseases

All Science Journal Classification (ASJC) codes

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

The role of mislocalized phototransduction in photoreceptor cell death of retinitis pigmentosa. / Nakao, Takeshi; Tsujikawa, Motokazu; Notomi, Shoji; Ikeda, Yasuhiro; Nishida, Kohji.

In: PloS one, Vol. 7, No. 4, e32472, 02.04.2012.

Research output: Contribution to journalArticle

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