Abstract
Purpose: :
To determine whether single or repeated treatments with α2-adrenergic agonist brimonidine protect against the loss of fluorescent retinal neurons in Thy1-CFP mice following optic nerve crush.Material and
Methods: :
Transgenic mice expressing cyan fluorescent protein under the control of a Thy-1 promoter (Thy1-CFP23Jrs) were randomly divided into 3 groups. In the first group, brimonidine (100 ug/kg) was administered by intraperitoneal injection one time immediately after optic nerve crush. In the second group, brimonidine (100 ug/kg) was administered immediately after optic nerve crush and then every 2 days for the remainder of the study. Mice treated with one saline injection were the control group. A blue-light confocal scanning laser ophthalmoscope (bCSLO) was used to image the retina of Thy1-CFP mice before optic nerve crush and weekly post crush for 3 weeks. Fluorescent neurons in corresponding retina areas imaged at each time point were counted manually.
Results: :
The proportion of fluorescent retinal neuron retaining fluorescence in the eyes of saline-treated animals was 43±7%, 31±7%, and 24±7% at 1, 2, and 3 weeks after optic nerve crush (n=10). In the group that received a single brimonidine injection at the time of the optic nerve crush, the proportion of fluorescent retinal neurons retaining fluorescence was greater by 18% at 1 week following optic nerve crush than in the eyes of the saline-treated animals (P<0.05, n=6). The difference between these treated eyes and the control eyes were insignificant at weeks 2 and 3 following optic nerve crush. In the group that received repeated injections of brimonidine, however, the proportion of fluorescent retinal neurons retaining fluorescence was greater by 27%, 28%, and 32% at 1, 2, and 3 weeks following optic nerve crush, respectively, than in the eyes of the saline-treated animals (P<0.05 at all time points, n=7).
Conclusions: :
Repeated brimonidine treatments provide sustained protection against fluorescent retinal neurons loss following optic nerve crush. As most of fluorescent retinal neurons detected by bCSLO are retinal ganglion cells (RGCs), these findings suggest that brimonidine may protect RGCs in optic neuropathies such as glaucoma.
Keywords: ganglion cells • imaging/image analysis: non-clinical • neuroprotection