April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
Serotonin 5-HT1A Agonists Protect Against Blue Light-Induced Phototoxicity
Author Affiliations & Notes
  • R. J. Collier
    Retina Drug Discovery, Alcon Research Ltd, Fort Worth, Texas
  • E. A. Martin
    Retina Drug Discovery, Alcon Research Ltd, Fort Worth, Texas
  • C. Cully-Adams
    Retina Drug Discovery, Alcon Research Ltd, Fort Worth, Texas
  • O. Dembinska
    Retina Drug Discovery, Alcon Research Ltd, Fort Worth, Texas
  • H. Hoang
    Retina Drug Discovery, Alcon Research Ltd, Fort Worth, Texas
  • M. Hellberg
    Retina Drug Discovery, Alcon Research Ltd, Fort Worth, Texas
  • S. Krueger
    Retina Drug Discovery, Alcon Research Ltd, Fort Worth, Texas
  • M. Kapin
    Retina Drug Discovery, Alcon Research Ltd, Fort Worth, Texas
  • C. Romano
    Retina Drug Discovery, Alcon Research Ltd, Fort Worth, Texas
  • Footnotes
    Commercial Relationships  R.J. Collier, Alcon Research, Ltd, E; E.A. Martin, Alcon Research, Ltd, E; C. Cully-Adams, Alcon Research, Ltd, E; O. Dembinska, Alcon Research, Ltd, E; H. Hoang, Alcon Research, Ltd, E; M. Hellberg, Alcon Research, Ltd, E; S. Krueger, Alcon Research, Ltd, E; M. Kapin, Alcon Research, Ltd, E; C. Romano, Alcon Research, Ltd, E.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 675. doi:
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      R. J. Collier, E. A. Martin, C. Cully-Adams, O. Dembinska, H. Hoang, M. Hellberg, S. Krueger, M. Kapin, C. Romano; Serotonin 5-HT1A Agonists Protect Against Blue Light-Induced Phototoxicity. Invest. Ophthalmol. Vis. Sci. 2009;50(13):675.

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

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Abstract

Purpose: : Determine whether serotonin 5-HT1A agonists can protect the rat retina from light induced injury.

Methods: : Three 5-HT1A agonists were evaluated: AL-8309A (IC50=25 nM), AL-12170 (IC50=19.6 nM) and 8-OH DPAT (IC50=1.5 nM). Albino rats were dosed (SQ) 2 days, 1 day, immediately before and 1 day after a 6-hr blue-light exposure (=450 nm, 3.1 X 103 mW/cm2). Control rats were not exposed to blue light. ERGs were measured to assess retinal function and retinal damage was evaluated by light microscopy (RPE and ONL thickness, photoreceptor segment length). In single dose experiments to determine protection onset and duration, 10mg/kg AL-8309A was dosed once before (72, 48, 24 or 0hrs), during (3hrs) or after light exposure (0hrs). Topical ocular dosing (b.i.d.) with 1.75% AL-8309B (OU) before light exposure was also evaluated.

Results: : Five days after light exposure, ERG a- and b-wave response amplitudes were significantly (p<0.05) depressed 70% in vehicle-dosed rats compared to controls. ERG a- and b-wave response amplitudes were significantly (p<0.05) higher in rats treated with AL-8309A (0.1-30 mg/kg), 8-OH DPAT (0.1-10 mg/kg) and AL-12170 (5-20 mg/kg) compared to vehicle-dosed rats. ERG response amplitudes were not different than controls in rats dosed with AL-8309A, when re-evaluated 1 month after light exposure. RPE thickness, ONL thickness and photoreceptor segment length in histological sections from these rats was also not different than controls.Significant (p<0.05) protection was measured in rats dosed once 0, 24 or 48 hours prior to light exposure. After topical ocular dosing with 1.75% AL-8309B,ERG responses were significantly (p=0.02) higher compared to vehicle-treated controls.

Conclusions: : Blue-light exposure for 6 hours resulted in significant retinal damage and reduction of the ERG response amplitude. These lesions were significantly reduced by treatment with all three 5-HT1A agonists evaluated. Lesions were completely ameliorated by AL-8309A. Single dose experiments with AL-8309A suggest that the mechanism of protection is rapidly activated and protection can persist for 48 hours. AL-8309B (1.75%) was effective after topical ocular dosing and may have utility in treating AMD.

Keywords: radiation damage: light/UV • neuroprotection • oxidation/oxidative or free radical damage 
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