Using in vitro and in vivo models of glaucoma, cannabinoids (CBs) demonstrated neuroprotection, stopped changes in extracellular matrix (ECM), and normalized intraocular pressure (IOP) levels in the eye, showing a possible therapeutic intervention for the irreversible eye disease, according to a study published in BBA Molecular Basis of Disease.

Since glaucoma is notable for progression in retinal ganglion cells (RGCs), a therapy is needed to stop that damage: Enter CBs, researchers say. Prior research has shown that CBs potentially lower IOP, helping stop RGC degeneration and optic nerve (ON) damage; however, the direct correlation of specific CBs with molecular events in glaucoma pathology has not been well established. Hence this study, which looked to better determine cannabinol’s (CBN) role in these factors with CBN and other CBs sourced from several locations used in the mouse 661W retinal ganglion precursor-like cell line and primary human TM (hTM) cells isolated from the juxtacanalicular and corneoscleral regions of the human eye.

Researchers found that when CBN (in a dose-dependent manner) was exposed to elevated hydrostatic pressure, it protected the differentiated mouse 661W cells from pressure-induced toxicity. And in the human trabecular meshwork cells (hTM), CBN “attenuated changes in ECM proteins,” which included fibronectin and α-smooth muscle actin (α-SMA), plus mitogen-activated protein kinases (phospho-ERK1/2) in the presence or absence of transforming growth factor-beta 2 (TGF-β2) induced stress. They also looked at ocular pharmacokinetic parameters 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,” they write.


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“Most of the current therapies available for glaucoma today provide an IOP-lowering effect and, indirectly, neuroprotection for the RGCs. There is an unmet medical need for improved glaucoma therapies that provide direct protection to RGC from degeneration. Such protection may improve the quality of life for the millions of people living with glaucoma by further reducing their risk of blindness,” researchers say. “The findings in this study demonstrate that CBN reduces IOP, attenuates TM remodeling and mediates effective protection of RGCs and their function both in vitro and in vivo. Overall, these results provide proof of concept supporting CBN’s potential as an important therapeutic agent for patients with glaucoma.”

Reference


Somvanshi RK, Zou S, Kadhim S, Padania S, Hsu E, Kumar U. Cannabinol modulates neuroprotection and intraocular pressure: A potential multi-target therapeutic intervention for glaucoma. Biochim Biophys Acta Mol Basis Dis. 2022;1868(3):166325. doi:10.1016/j.bbadis.2021.166325