doi: 10.1016/j.bbadis.2021.166325. Online ahead of print.
- PMID: 34921975
- DOI: 10.1016/j.bbadis.2021.166325
Abstract
Objectives: Glaucoma is characterized by progressive damage of the retinal ganglion cells (RGC), resulting in irreversible vision loss. Cannabinoids (CBs) ameliorate several factors that contribute to the progression of glaucoma, including increased intraocular pressure (IOP), degeneration of RGC and optical nerve (ON) damage. However, a direct correlation of specific CBs with the molecular events pertaining to glaucoma pathology is not well established. Therefore, this study aims to evaluate the role of cannabinol (CBN) on RGC protection, modulation of IOP, and its effects on the level of extracellular matrix (ECM) proteins using both in vitro and in vivo models of glaucoma.
Methods and results: When exposed to elevated hydrostatic pressure, CBN, in a dose-dependent manner, protected differentiated mouse 661W retinal ganglion precursor-like cells from pressure-induced toxicity. In human trabecular meshwork cells (hTM), CBN attenuated changes in the ECM proteins, including fibronectin and α-smooth muscle actin (α-SMA), as well as mitogen-activated protein kinases (phospho-ERK1/2) in the presence or absence of transforming growth factor-beta 2 (TGF-β2) induced stress. Ocular pharmacokinetic parameters were evaluated post-intravitreal (IVT) CBN delivery in vivo. Furthermore, we demonstrated that IVT-administered CBN improved pattern electroretinogram (pERG) amplitudes and reduced IOP in a rat episcleral vein laser photocoagulation model of glaucoma.
Conclusion: CBN promotes neuroprotection, abrogates changes in ECM protein, and normalizes the IOP levels in the eye. Therefore, our observations in the present study indicate a therapeutic potential for CBN in the treatment of glaucoma.
Keywords: Cannabinol, Glaucoma, Intraocular pressure, Neuroprotection, Pattern electroretinogram, Retinal ganglion cells, Trabecular meshwork
Copyright © 2021. Published by Elsevier B.V.
Conflict of interest statement
Declaration of competing interest Ujendra Kumar reports financial support was provided by InMed Pharmaceuticals Inc. Rishi K Somvanshi reports financial support was provided by InMed Pharmaceuticals Inc. Shenglong Zou reports financial support was provided by MITACs Canada/InMed Pharmaceuticals Inc. InMed Pharmaceuticals is commercializing cannabinoid-based therapies. Eric Hsu is the Senior Vice President, Salam Kadhim is Senior Scientist of Preclinical R&D, and Sapna Padania is Scientist II at InMed Pharmaceuticals Inc. Rishi K Somvanshi is a Research Consultant. Eric Hsu, Ujendra Kumar, Rishi K Somvanshi and Shenglong Zou has patent – Compositions and Methods for the use of Cannabinoids for Neuroprotection, issued to InMed Pharmaceuticals Inc.
