Inducible ablation of melanopsin-expressing retinal ganglion cells reveals their central role in non-image forming visual responses

Megumi Hatori, Hiep Le, Christopher Vollmers, Sheena Racheal Keding, Nobushige Tanaka, Christian Schmedt, Timothy J. Jegla, Satchidananda Panda

Research output: Contribution to journalArticle

164 Citations (Scopus)

Abstract

Rod/cone photoreceptors of the outer retina and the melanopsin-expressing retinal ganglion cells (mRGCs) of the inner retina mediate non-image forming visual responses including entrainment of the circadian clock to the ambient light, the pupillary light reflex (PLR), and light modulation of activity. Targeted deletion of the melanopsin gene attenuates these adaptive responses with no apparent change in the development and morphology of the mRGCs. Comprehensive identification of mRGCs and knowledge of their specific roles in image-forming and non-image forming photoresponses are currently lacking. We used a Cre-dependent GFP expression strategy in mice to genetically label the mRGCs. This revealed that only a subset of mRGCs express enough immunocytochemically detectable levels of melanopsin. We also used a Cre-inducible diphtheria toxin receptor (iDTR) expression approach to express the DTR in mRGCs. mRGCs develop normally, but can be acutely ablated upon diptheria toxin administration. The mRGC-ablated mice exhibited normal outer retinal function. However, they completely lacked non-image forming visual responses such as circadian photoentrainment, light modulation of activity, and PLR. These results point to the mRGCs as the site of functional integration of the rod/cone and melanopsin phototransduction pathways and as the primary anatomical site for the divergence of image-forming and non-image forming photoresponses in mammals.

Original languageEnglish (US)
Article numbere2451
JournalPloS one
Volume3
Issue number6
DOIs
StatePublished - Jun 11 2008

Fingerprint

Retinal Ganglion Cells
Ablation
cells
rods (retina)
Light
cones (retina)
Pupillary Reflex
reflexes
retina
Vertebrate Photoreceptor Cells
Light modulation
toxins
phototransduction
Retina
melanopsin
Cones
gene deletion
mice
Light Signal Transduction
Retinal Cone Photoreceptor Cells

All Science Journal Classification (ASJC) codes

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

Cite this

Hatori, Megumi ; Le, Hiep ; Vollmers, Christopher ; Keding, Sheena Racheal ; Tanaka, Nobushige ; Schmedt, Christian ; Jegla, Timothy J. ; Panda, Satchidananda. / Inducible ablation of melanopsin-expressing retinal ganglion cells reveals their central role in non-image forming visual responses. In: PloS one. 2008 ; Vol. 3, No. 6.
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abstract = "Rod/cone photoreceptors of the outer retina and the melanopsin-expressing retinal ganglion cells (mRGCs) of the inner retina mediate non-image forming visual responses including entrainment of the circadian clock to the ambient light, the pupillary light reflex (PLR), and light modulation of activity. Targeted deletion of the melanopsin gene attenuates these adaptive responses with no apparent change in the development and morphology of the mRGCs. Comprehensive identification of mRGCs and knowledge of their specific roles in image-forming and non-image forming photoresponses are currently lacking. We used a Cre-dependent GFP expression strategy in mice to genetically label the mRGCs. This revealed that only a subset of mRGCs express enough immunocytochemically detectable levels of melanopsin. We also used a Cre-inducible diphtheria toxin receptor (iDTR) expression approach to express the DTR in mRGCs. mRGCs develop normally, but can be acutely ablated upon diptheria toxin administration. The mRGC-ablated mice exhibited normal outer retinal function. However, they completely lacked non-image forming visual responses such as circadian photoentrainment, light modulation of activity, and PLR. These results point to the mRGCs as the site of functional integration of the rod/cone and melanopsin phototransduction pathways and as the primary anatomical site for the divergence of image-forming and non-image forming photoresponses in mammals.",
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Inducible ablation of melanopsin-expressing retinal ganglion cells reveals their central role in non-image forming visual responses. / Hatori, Megumi; Le, Hiep; Vollmers, Christopher; Keding, Sheena Racheal; Tanaka, Nobushige; Schmedt, Christian; Jegla, Timothy J.; Panda, Satchidananda.

In: PloS one, Vol. 3, No. 6, e2451, 11.06.2008.

Research output: Contribution to journalArticle

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AU - Hatori, Megumi

AU - Le, Hiep

AU - Vollmers, Christopher

AU - Keding, Sheena Racheal

AU - Tanaka, Nobushige

AU - Schmedt, Christian

AU - Jegla, Timothy J.

AU - Panda, Satchidananda

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