April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Protective Effect of Oral OT-440 Against Loss of Fluorescent Retinal Neurons in Thy1-CFP Mice Following Optic Nerve Crush
Author Affiliations & Notes
  • J. D. Lindsey
    Hamilton Glaucoma Center - Ophthalmology, Univ of California-San Diego, La Jolla, California
  • K. X. Duong-Polk
    Hamilton Glaucoma Center - Ophthalmology, Univ of California-San Diego, La Jolla, California
  • Y. Dai
    Hamilton Glaucoma Center - Ophthalmology, Univ of California-San Diego, La Jolla, California
  • C. K. S. Leung
    University Eye Center, Chinese University of Hong Kong, Hong Kong, Hong Kong
  • G. Patil
    Clinical Development, Othera Pharmaceuticals, Inc, Conshohocken, Pennsylvania
  • A. Reaves
    Clinical Development, Othera Pharmaceuticals, Inc, Conshohocken, Pennsylvania
  • D. Nguyen
    Hamilton Glaucoma Center - Ophthalmology, Univ of California-San Diego, La Jolla, California
  • R. N. Weinreb
    Hamilton Glaucoma Center - Ophthalmology, Univ of California-San Diego, La Jolla, California
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 3174. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      J. D. Lindsey, K. X. Duong-Polk, Y. Dai, C. K. S. Leung, G. Patil, A. Reaves, D. Nguyen, R. N. Weinreb; Protective Effect of Oral OT-440 Against Loss of Fluorescent Retinal Neurons in Thy1-CFP Mice Following Optic Nerve Crush. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3174.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose: : To determine whether oral treatment with the water-soluble hydroxylamine derivative OT-440 protects against loss of fluorescent retinal neurons in Thy1-CFP mice following optic nerve crush.

Methods: : Transgenic mice expressing cyan fluorescent protein under the control of the promoter for Thy-1 (Thy1-CFP mice) were imaged using a blue-light confocal scanning laser ophthalmoscope (bCSLO), started on oral OT-440 treatments or vehicle (mixed with cream cheese 3x/day or by gavage 2x/day) for two weeks, imaged by blue light scanning laser ophthalmoscopy (bCSLO), and then all animals received unilateral optic nerve crush. Oral OT-440 treatments continued uninterrupted for the next four weeks while bCSLO imaging was performed weekly for four weeks starting one week after the crush. Fluorescent neurons in defined retinal areas imaged at each time point were counted in a masked fashion.

Results: : Two-week treatment with OT-440 by cream cheese or by gavage alone produced no change in the number of fluorescent neurons (P>0.4). The numbers of fluorescent retinal cells were greater in mice fed cream cheese containing OT-440 than in control mice by 7.5%, 27%, 52%, and 60% at 1, 2, 3, and 4 weeks after optic nerve crush, respectively (P<0.001 at weeks 2, 3, and 4). The numbers of fluorescent retinal cells in mice that received OT-411 via gavage were greater by 27%, 24%, 28% and 40% at 1, 2, 3, or 4 weeks after optic nerve crush than in mice that received vehicle (P<0.04 at all time points). Body weight changes over the course of study were insignificant (P>0.5).

Conclusions: : Oral treatment with OT-440 protects against loss of fluorescent retinal neurons of Thy1-CFP mice following optic nerve crush. As most of the fluorescent cells detected by bCSLO are RGCs, these findings suggest that oral OT-440 could protect vision in optic neuropathies such as glaucoma.

Keywords: neuroprotection • antioxidants • imaging/image analysis: 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.

×