June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Sunitinib promotes the survival and function of photoreceptors in the murine light damage model
Author Affiliations & Notes
  • Byung-Jin Kim
    Ophthalmology, Johns Hopkins University, School of Medicine, Baltimore, MD
  • Tomohiro Masuda
    Ophthalmology, Johns Hopkins University, School of Medicine, Baltimore, MD
  • Gillian C. Shaw
    Ophthalmology, Johns Hopkins University, School of Medicine, Baltimore, MD
  • Cynthia A Berlinicke
    Ophthalmology, Johns Hopkins University, School of Medicine, Baltimore, MD
  • Donald J Zack
    Ophthalmology, Johns Hopkins University, School of Medicine, Baltimore, MD
  • Footnotes
    Commercial Relationships Byung-Jin Kim, None; Tomohiro Masuda, None; Gillian Shaw, None; Cynthia Berlinicke, Johns Hopkins University (F), Johns Hopkins University (P); Donald Zack, Johns Hopkins University (F), Johns Hopkins University (P)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 3609. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Byung-Jin Kim, Tomohiro Masuda, Gillian C. Shaw, Cynthia A Berlinicke, Donald J Zack; Sunitinib promotes the survival and function of photoreceptors in the murine light damage model. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3609.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose: Although gene-specific therapies are being developed for some forms of retinal degeneration (RD), an alternative and complementary approach is to develop neuroprotective compounds that support the survival of photoreceptors (PRs) independent of the specific disease-causing mutation. Based on our prior finding that the FDA-approved multi-kinase inhibitor sunitinib is neuroprotective for RGCs, we tested if sunitinib could promote PR survival and function in the light damage (LD) model of RD.

Methods: 12 week old female Balbc/J mice were acclimated in dim light (~ 10 lux) for 14 days. Sunitinib (15, 30 and 60 mg/kg) or vehicle (5% DMSO in PBS) were administered by daily intraperitoneal injection starting 48 h prior to LD. After dark adaptation, mice were placed in light chamber (~3000 lux) for 4 h followed by immediate dark recovery. Serial SD-OCT imaging, immunohistochemistry, and scotopic flash ERG were used to assess retinal structure and function.

Results: By day 6 post LD, retinal outer layer (ROL) thickness (from OPL to inner PR edge) of vehicle group was significantly decreased (44.78 ± 0.03%, P<0.001) in comparison with baseline imaging prior to LD (defined as 100 %), with no significant changes in the inner layers. LD also induced significant (P<0.01) decrease in ERG a wave (89.99 ± 4.99 %) and b wave (75.61 ± 6.94 %) by day 6 post LD compared to baseline amplitude measured 96 h prior to LD. Administration of sunitinib at 60 mg/kg attenuated LD-induced ROL thinning up to the latest time point tested (6 days post LD) in contrast to vehicle-administered group. Additionally, with sunitinib 60 mg/kg no significant decrease in ERG b wave amplitude was observed by day 6 post LD, although ERG a wave was decreased to 50.46 ± 33.09 % (P<0.05). 60 mg/kg sunitinib also reduced the decrease in rhodopsin and cone arrestin expression observed after LD. 30 mg/kg sunitinib showed a trend toward neuroprotection, but the magnitude of the effects were lower than that observed with 60 mg/kg.

Conclusions: Our data demonstrates that sunitinib (60 mg/kg) promotes PR survival and function following light exposure-induced PR damage. We are working to define the molecular target(s) that mediate sunititib’s neuroprotective activity on PRs. We are also testing sunitinib in other models of RD.

×
×

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.

×