May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Effects of a Vitamin-A Derivative (AG-787-14-2) on Retinal Function in Oxygen-Induced Retinopathy
Author Affiliations & Notes
  • J. D. Akula
    Ophthalmology, Children's Hospital, Boston, Massachusetts
    Harvard Medical School, Boston, Massachusetts
  • R. Kubota
    Acucela Inc., Bothell, Washington
  • R. M. Hansen
    Ophthalmology, Children's Hospital, Boston, Massachusetts
    Harvard Medical School, Boston, Massachusetts
  • R. Tzekov
    Acucela Inc., Bothell, Washington
  • D. McGee
    Acucela Inc., Bothell, Washington
  • A. B. Fulton
    Ophthalmology, Children's Hospital, Boston, Massachusetts
    Harvard Medical School, Boston, Massachusetts
  • Footnotes
    Commercial Relationships  J.D. Akula, Acucela, Inc., F; R. Kubota, Acucela Inc., E; R.M. Hansen, None; R. Tzekov, Acucela Inc., E; D. McGee, Acucela Inc., E; A.B. Fulton, None.
  • Footnotes
    Support  The Pearle Vision Foundation and Acucela, Inc.
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 2629. doi:https://doi.org/
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      J. D. Akula, R. Kubota, R. M. Hansen, R. Tzekov, D. McGee, A. B. Fulton; Effects of a Vitamin-A Derivative (AG-787-14-2) on Retinal Function in Oxygen-Induced Retinopathy. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2629. doi: https://doi.org/.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose: : Rats with oxygen-induced retinopathy (OIR) are a common model of human retinopathy of prematurity (ROP). Both OIR and ROP are characterized by abnormal retinal vasculature and by lasting dysfunction of the neural retina. Our recent findings in OIR rats imply a causal role for the rods in the ROP disease process. However, experimental manipulation of rod function is necessary to establish this role conclusively. We hypothesized that Acucela Inc.’s vitamin-A derivative, AG-787-14-2 (the "drug"), would alter rod function in OIR.

Methods: : OIR was induced in four litters of Sprague-Dawley pups (N=24) by exposure to alternating periods of 50% and 10% oxygen from the day of birth (P0) to P14. The light cycle was 12 hr light (10-30 lux) and 12 hr dark; the light-to-dark transition coincided with each oxygen alternation. For 15 days beginning P7, within one hour of this transition, the first and fourth litters were administered 6 mg/kg drug IP; the second and third litters received only vehicle. At P20-22, when marked retinal vascular abnormality is generally observed, electroretinograms were recorded and receptor and post-receptor function evaluated. Treatment effects were evaluated by ANOVA.

Results: : Neither the maximal rod response nor the amplification constant of phototransduction were much changed by the drug treatment. However, the time-constant of deactivation of phototransduction, assessed by a double-flash protocol, was significantly shorter in drug-treated rats. Intriguingly, differences in post-receptoral responses were marked. While post-receptor sensitivity (log σ) was unchanged, maximal scotopic b-wave amplitude was twice as large in drug-treated as vehicle-treated rats. The OFF response to a 400 ms stimulus presented in the presence of a background that suppressed the saturating a-wave by ~90% was likewise 2× larger, as was the cone-driven response to 20 Hz flicker presented on the same background.

Conclusions: : There was no evidence of serious, negative alteration of the photoreceptor response after treatment with AG-787-14-2. Importantly, the drug appears to have had a favorable effect on responses originating in the inner retina. The inner retina is supplied by the retinal vasculature; quantitative image analysis of fundus photographs will ascertain if the vascular abnormality associated with OIR was, in turn, reduced.

Keywords: retinopathy of prematurity • oxidation/oxidative or free radical damage • electroretinography: non-clinical 
×
×

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.

×