Abstract
Purpose :
Glaucoma is a group of progressive irreversible optic neuropathies that is associated with retinal ganglion cell (RGC) death and blindness. Currently, the only proven therapy for glaucoma is to reduce intraocular pressure (IOP) to preserve RGC survival and visual function. The optic nerve neuroprotection of brimonidine, an alpha-2 adrenergic agonist, has been reported in some animal models. Recently, live cell imaging methods of measuring RGC function was published. Here, we used this noninvasive in vivo Ca2+ imaging of RGCs to assess the neuroprotective properties of brimonidine after an optic nerve crush (ONC) model.
Methods :
Using AAV2-mSncg-jGCaMP7, wild type c57b/6j mice eyes were given intravitreal injection and RGCs transduced with the live cell Ca2+ tracer. The mouse optic nerve crush was performed 3 weeks later, followed by topical brimonidine and placebo treatment 3 times daily for two weeks. The calcium signal of RGC was recorded through Heidelberg cSLO system after AAV2-mSncg-jGCaMP7s injection. Retinal thickness, IOP, and pattern electroretinogram (PERG) were also examined at baseline and 3, 7, 14 d after treatment. Retinas were collected for RGC quantification by RBPMS immunostaining.
Results :
There was a significant decrease in RGC number (236.66±9.60 vs 51.33±9.07, p < 0.001) with a survival rate of 21% at 14 d after ONC as compared with controls. The amplitude and cell count of ON-RGCs also decreased significantly (234.76±27.30 vs 45.31±16.65, p = 0.005, student t-test). Interestingly, many ON-RGCs converted to OFF-RGCs after ONC. Additionally, the retinal thickness increased at 3 d after treatment due to the inflammation induced by ONC. However, no significant difference was found in IOP, retinal thickness and PERG between eyes with and without brimonidine treatment.
Conclusions :
The topical use of brimonidine eye drops does not exhibit functional protection on RGC function and survival, measured by live-cell calcium imaging, in a ONC model.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.