May 2003
Volume 44, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2003
Prevention of Photic-Induced Retinopathy with 8-OH-DPAT
Author Affiliations & Notes
  • R. Collier
    Retinopathy-Degen Dis, Alcon Research Ltd, Fort Worth, TX, United States
  • E. Martin
    Retinopathy-Degen Dis, Alcon Research Ltd, Fort Worth, TX, United States
  • R. Landers
    Retinopathy-Degen Dis, Alcon Research Ltd, Fort Worth, TX, United States
  • C. Cully
    Retinopathy-Degen Dis, Alcon Research Ltd, Fort Worth, TX, United States
  • Y. Patel
    Retinopathy-Degen Dis, Alcon Research Ltd, Fort Worth, TX, United States
  • S. Krueger
    Retinopathy-Degen Dis, Alcon Research Ltd, Fort Worth, TX, United States
  • Footnotes
    Commercial Relationships  R. Collier, Alcon Research, Ltd E; E. Martin, Alcon Research, Ltd E; R. Landers, Alcon Research, Ltd E; C. Cully, Alcon Research, Ltd E; Y. Patel, Alcon Research, Ltd E; S. Krueger, Alcon Research, Ltd E.
Investigative Ophthalmology & Visual Science May 2003, Vol.44, 5246. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      R. Collier, E. Martin, R. Landers, C. Cully, Y. Patel, S. Krueger; Prevention of Photic-Induced Retinopathy with 8-OH-DPAT . Invest. Ophthalmol. Vis. Sci. 2003;44(13):5246.

      Download citation file:


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

      ×
  • Supplements
Abstract

Abstract: : Purpose: Eliprodil (AL-4043), a potent NMDA antagonist, has been shown to protect retinal photoreceptors from oxidative injury. In this study, the potency of AL-4043 and its R (AL-4822) and S (AL-4821) isomers were compared to receptor binding data to elucidate potential mechanisms of protection. Based on the efficacy and receptor binding profiles of these molecules, 5-HT1A agonist activity was evaluated. Methods: Albino rats were dosed (IP) with eliprodil or its isomers (0 to 80 mg/kg) 48, 24 and 0 hrs prior to a 6-hr blue-light exposure (220fc). ERGs were measured after a 5-day recovery period. Additionally, rats were dosed with a 5-HT1A agonist, 8-OH-DPAT (0, 0.5, and 1.0 mg/kg), prior to light exposure. Retinal function was assessed after a 5-day recovery period. Retinal lesions were evaluated 3 weeks later. Results: Compared to normals, ERG responses from vehicle-dosed light-exposed rats were significantly depressed (70%). Significant protection of retinal function was measured with AL-4821 (10 mg/kg), AL-4043 (20 mg/kg) and AL-4822 (40 mg/kg). Binding affinity (IC50, nM) for the NMDA receptor was >10,000 (S-), 380 (R,S-) and 320 (R-isomer). At the 5-HT1A receptor, the IC50s (nM) were 111, 191, and 1840, respectively. Treatment with 8-OH-DPAT resulted in significant preservation of retinal function and structure in rats dosed with 1 mg/kg. ERG a-wave response amplitudes were 50% of normal and the ONL was significantly thicker compared to vehicle dosed rats and not different from normal. Conclusions: The neuroprotective activity measured with eliprodil and its isomers did not follow its binding efficacy to the NMDA receptor; however, its activity appeared to be related to its binding affinity to the 5-HT1A receptor. Treatment with a 5-HT1A agonist demonstrated marked potency and suggests a novel approach to treatment of retinal disease.

Keywords: radiation damage: light/UV • photoreceptors • neuroprotection 
×
×

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.

×