1. Academic Validation
  2. Ciliary neurotrophic factor (CNTF) protects retinal cone and rod photoreceptors by suppressing excessive formation of the visual pigments

Ciliary neurotrophic factor (CNTF) protects retinal cone and rod photoreceptors by suppressing excessive formation of the visual pigments

  • J Biol Chem. 2018 Sep 28;293(39):15256-15268. doi: 10.1074/jbc.RA118.004008.
Songhua Li 1 Kota Sato 1 William C Gordon 1 2 Michael Sendtner 3 Nicolas G Bazan 1 2 Minghao Jin 4 2
Affiliations

Affiliations

  • 1 From the Neuroscience Center of Excellence and.
  • 2 Department of Ophthalmology, Louisiana State University School of Medicine, New Orleans, Louisiana 70112 and.
  • 3 the Institute of Clinical Neurobiology, University Hospital Würzburg, D-97078 Würzburg, Germany.
  • 4 From the Neuroscience Center of Excellence and mjin@lsuhsc.edu.
Abstract

The retinal pigment epithelium (RPE)-dependent visual cycle provides 11-cis-retinal to opsins in the photoreceptor outer segments to generate functional visual Pigments that initiate phototransduction in response to LIGHT stimuli. Both RPE65 isomerase of the visual cycle and the rhodopsin visual pigment have recently been identified as critical players in mediating light-induced retinal degeneration. These findings suggest that the expression and function of RPE65 and rhodopsin need to be coordinately controlled to sustain normal vision and to protect the retina from photodamage. However, the mechanism controlling the development of the retinal visual system remains poorly understood. Here, we show that deficiency in ciliary neurotrophic factor (CNTF) up-regulates the levels of rod and cone opsins accompanied by an increase in the thickness of the outer nuclear layers and the lengths of cone and rod outer segments in the mouse retina. Moreover, retinoid isomerase activity, expression levels of RPE65 and lecithin:retinol Acyltransferase (LRAT), which synthesizes the RPE65 substrate, were also significantly increased in the CNTF-/- RPE. Rod a-wave and cone b-wave amplitudes of electroretinograms were increased in CNTF-/- mice, but rod b-wave amplitudes were unchanged compared with those in WT mice. Up-regulated RPE65 and LRAT levels accelerated both the visual cycle rate and recovery rate of rod LIGHT sensitivity in CNTF-/- mice. Of note, rods and cones in CNTF-/- mice exhibited hypersusceptibility to light-induced degeneration. These results indicate that CNTF is a common extracellular factor that prevents excessive production of opsins, the photoreceptor outer segments, and 11-cis-retinal to protect rods and cones from photodamage.

Keywords

CNTF; RPE65; electroretinography; opsin; photoreceptor; phototransduction; retinal degeneration; retinoid; vision; visual cycle.

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