June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
VSN16S, an agonist of the cannabinoid receptor, reduces IOP profiles and exhibits neuroprotective properties in a rat model of glaucoma
Author Affiliations & Notes
  • Li Guo
    Institute of Ophthalmology, University College London, London, London, United Kingdom
  • Vy Luong
    Institute of Ophthalmology, University College London, London, London, United Kingdom
  • Aaron Gregson
    Medicinal Chemistry, Wolfson Institute for Biomedical Research, University College London, London, London, United Kingdom
  • David Baker
    Neuroimmunology Unit, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, London, United Kingdom
  • David Selwood
    Medicinal Chemistry, Wolfson Institute for Biomedical Research, University College London, London, London, United Kingdom
  • M Francesca Cordeiro
    Institute of Ophthalmology, University College London, London, London, United Kingdom
    ICORG, Western Eye Hospital, London, London, United Kingdom
  • Footnotes
    Commercial Relationships   Li Guo, None; Vy Luong, None; Aaron Gregson, None; David Baker, None; David Selwood, None; M Francesca Cordeiro, Novai Ltd (I)
  • Footnotes
    Support  Fight for Sight Grant 1858/1859
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 2360. doi:
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      Li Guo, Vy Luong, Aaron Gregson, David Baker, David Selwood, M Francesca Cordeiro; VSN16S, an agonist of the cannabinoid receptor, reduces IOP profiles and exhibits neuroprotective properties in a rat model of glaucoma. Invest. Ophthalmol. Vis. Sci. 2021;62(8):2360.

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

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Abstract

Purpose : There is an unmet need for new drugs in glaucoma that can effectively prevent glaucoma progression. We assessed the effects of VSN16S and AG-020, the agonists of the cannabinoid receptor, on intraocular pressure (IOP) and neuroprotection using a rat model of ocular hypertension (OHT).

Methods : 20 male Dark Agouti (DA) rats aged 8-10 weeks were randomly located into four groups (n=5): OHT-only, OHT+vehicle, OHT+VSN16S, and OHT+AG-020. All animals had IOP surgically elevated in the left eye (OS) by injection of hypertonic saline into the episcleral veins. Except for OHT-only, animals in the other three groups have received eye drops in OS either vehicle or VSN16S or AG-0202 at 10mg/ml, twice daily for 3 weeks following OHT-induction. IOPs were recorded in both eyes at baseline (BL), day1, week1, 2, and 3 using a Tonopen. Animals were in vivo imaged for retinal ganglion cell (RGC) apoptosis in both eyes using DARC (Detection of Apoptotic Retinal Cells) at BL and week3 before culled. Retinal whole-mounts were immunostained with a Brn-3a antibody to assess RGC survival. DARC spots and RGC counts were assessed by blinded algorithm analysis.

Results : Surgical procedure induced a significant increase in IOP profiles in all animal groups compared to the contralateral eye (OD), and peak levels occurred at day1 (p<0.001). In the OHT eyes treated with VSN16S, IOPs at week1 exhibited a sharp reduction (p<0.05), and integrate IOP at week3 was significantly lower than vehicle controls (p<0.01). However, AG020 showed no effect on IOP. Surgically induced IOP elevation resulted in a significant increase in DARC counts (RGC apoptosis) in all groups, compared to the baseline. DARC counts revealed a significant reduction in the OHT eyes treated by VSN16S, compared to the OHT-only and vehicle groups (p<0.01), but less of a reduction of DARC counts was observed with AG-020 treatment (p<0.05). A significant reduction of Brn-3a+RGC density was seen in the OHT-only group compared to naïve controls (p<0.05), and VSN16S treatment demolished the difference although no significance was found on Brn-3a+RGC density between VSN16S and controls.

Conclusions : VSN16S exerted neuroprotective properties in OHT-induced RGC loss, which may be associated with lowering IOP profiles. DARC is a useful tool in the assessment of drug efficacy in retinal neurodegenerative diseases.

This is a 2021 ARVO Annual Meeting abstract.

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