June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
CNTF treatment prevents development of pathological tuft formation in VLDLR -/- mice
Author Affiliations & Notes
  • Edith Aguilar
    Cell Biology, Scripps Research Institute, Del Mar, California, United States
  • Felicitas Bucher
    Cell Biology, Scripps Research Institute, Del Mar, California, United States
  • Mauricio Rosenfeld
    Cell Biology, Scripps Research Institute, Del Mar, California, United States
  • Susumu Sakimoto
    Cell Biology, Scripps Research Institute, Del Mar, California, United States
  • Salome Murinello
    Cell Biology, Scripps Research Institute, Del Mar, California, United States
  • Marin Gantner
    The Lowy Medical Research Institute, San Diego, California, United States
  • kevin eade
    The Lowy Medical Research Institute, San Diego, California, United States
  • Sophia Diaz-Aguilar
    Cell Biology, Scripps Research Institute, Del Mar, California, United States
  • Maki Kitano
    Cell Biology, Scripps Research Institute, Del Mar, California, United States
  • Martin Friedlander
    Cell Biology, Scripps Research Institute, Del Mar, California, United States
    The Lowy Medical Research Institute, San Diego, California, United States
  • Footnotes
    Commercial Relationships   Edith Aguilar, None; Felicitas Bucher, None; Mauricio Rosenfeld, None; Susumu Sakimoto, None; Salome Murinello, None; Marin Gantner, None; kevin eade, None; Sophia Diaz-Aguilar, None; Maki Kitano, None; Martin Friedlander, None
  • Footnotes
    Support  Martin Fiedlander: NEI Grant (EY11254) and the Lowy Medical Research Institute, Felicitas Bucher: German Research Foundation (Bu 3135/1-1)
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 189. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      Edith Aguilar, Felicitas Bucher, Mauricio Rosenfeld, Susumu Sakimoto, Salome Murinello, Marin Gantner, kevin eade, Sophia Diaz-Aguilar, Maki Kitano, Martin Friedlander; CNTF treatment prevents development of pathological tuft formation in VLDLR -/- mice. Invest. Ophthalmol. Vis. Sci. 2017;58(8):189.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : Ciliary neurotrophic factor (CNTF) is one of the best studied neurotrophic agents and is currently in clinical trials for the treatment of retinitis pigmentosa and macular telangiectasia. Recent studies suggest that CNTF provides angio-modulatory effects in ischemic retinopathies. In this study, we tested the effect of CNTF on pathological tuft formation in VLDLR -/- knockout mice and explored the mechanism behind the angio-modulatory effect of CNTF treatment.

Methods : VLDLR -/- knock-out mice received intravitreal injections with recombinant rat CNTF (rrCNTF) at postnatal day 12 (P12) or P19. Intraretinal tuft formation was quantified at P18 or P34. Western blot and qPCR analysis of whole retina lysates were performed to identify downstream signaling pathways activated by CNTF treatment. Immunhistochemical stainings were used to identify CNTF responsive cells. In vitro experiments with primary mouse Müller cells were performed to explore the effect of CNTF on these cells.

Results : Intravitreal injections of rrCNTF at P12 significantly decreased intraretinal tuft formation at P18 and P34 while treatment at later time points (P18) did not reduce the number of intraretinal tufts. Peri-neovascular regions in VLDLR -/- mice showed a decrease in opsin staining in untreated, as well as rrCNTF treated eyes. CNTF treatment strongly induced phosphorylation of signal transducer and activator of transcription 3 (STAT3) 6 hours post injection and increased overall retinal expression levels of STAT3 up to 6 days post injection. Immunhistochemical analysis detected pSTAT3 signals in the inner nuclear layer. In vitro experiments confirmed that Müller cells respond to CNTF treatment with phosphorylation of STAT3.

Conclusions : CNTF treatment shows significant therapeutic potential for retinal neovascular disease. While CNTF treatment effectively prevented intraretinal tuft formation, it could not reduce pre-existing vascular abnormalities. Mechanistic studies showed that CNTF treatment did not prevent localized photoreceptor loss in the peri-neovascular regions of VLDLR -/- retinas. Activation of the Jak/STAT3 signaling pathway following CNTF treatment was detected in retinal Müller, but not photoreceptor, cells suggesting that the anti-angiogenic effect observed in VLDLR -/- is at least partially Müller-cell mediated.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×