Purchase this article with an account.
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)
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.
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.
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).
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.
This PDF is available to Subscribers Only