June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Effect of Brimonidine on Retinal Ganglion Cell Function by in vivo Calcium Imaging in Glaucoma Mice Model
Author Affiliations & Notes
  • Tingting Li
    Ophthalmology, Stanford University School of Medicine, Stanford, California, United States
    Ophthalmology, Shanghai Tenth People's Hospital, Shanghai, China
  • QING WANG
    Ophthalmology, Stanford University School of Medicine, Stanford, California, United States
  • Chien-Hui Lo
    Ophthalmology, Stanford University School of Medicine, Stanford, California, United States
  • Ke Ning
    Ophthalmology, Stanford University School of Medicine, Stanford, California, United States
  • Rishab Majumder
    Ophthalmology, Stanford University School of Medicine, Stanford, California, United States
  • Yang Sun
    Ophthalmology, Stanford University School of Medicine, Stanford, California, United States
  • Footnotes
    Commercial Relationships   Tingting Li None; QING WANG None; Chien-Hui Lo None; Ke Ning None; Rishab Majumder None; Yang Sun None
  • Footnotes
    Support  NIH R01-EY025295 (Y.S.), R01 EY032159 (Y.S), Veteran Affairs Merit Award CX001481 (Y.S.), Stanford Maternal and Children’s Health Research Institute Lacob Faculty Scholar Award (Y.S.). the NIH NEI P30 Vision Research Core (EY026877, Stanford Ophthalmology), and an unrestricted grant from Research to Prevent Blindness (Stanford Ophthalmology)
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 4713. doi:
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      Tingting Li, QING WANG, Chien-Hui Lo, Ke Ning, Rishab Majumder, Yang Sun; Effect of Brimonidine on Retinal Ganglion Cell Function by in vivo Calcium Imaging in Glaucoma Mice Model. Invest. Ophthalmol. Vis. Sci. 2023;64(8):4713.

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

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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.

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