Systemic administration with tetrahydrocannabinol causes retinal damage in BALB/c mice

Abstract

Recent years have seen substantial shifts in cultural attitudes towards cannabis for medical and recreational use. However, legalizing recreational marijuana may have adverse effects on individual and public health. As the most widely used illicit agent, cannabis is commonly reported to disrupt learning and memory. Unfortunately, the molecular mechanisms underlying behavioral impairment by cannabis abuse remain poorly understood. Tetrahydrocannabinol (THC), a major component in cannabis, causes short-term effects on the visual system, but little is known about persisting visual disturbances. This study was to investigate the effects of systemic administration with THC on retina and explore its underlying mechanisms. BALB/c mice were treated with 1 or 2 mg/kg THC intraperitoneally daily for 2 months, mice treated with vehicle as negative control. The retinal function was tested by electroretinography after THC treatment. Morphology and pathology changes of retina were detected by hematoxylin and eosin staining. Terminal deoxynucleotidyl transferase dUTP nick end labeling assay was used to detect the apoptosis in photoreceptor cells. Enzyme-linked immunosorbent assay was used to show the inflammatory responses and oxidative stress. mRNA and protein changes were measured by real-time polymerase chain reaction and Western blot to explore the underlying mechanisms. Results indicated that 2-month treatment with THC caused retinal damage, evidenced by its functional loss and increased apoptosis in photoreceptor cells through inducing inflammatory responses and oxidative stress. Our study demonstrated that systemic administration with THC caused toxic effects on retinas of BALB/c mice, suggesting the potential mechanisms for the retina damage caused by cannabis abuse.

Lasting effects of prenatal exposure to Cannabis in the retina of the offspring: an experimental study in mice

“…An experimental study using adult BALB/c mice showed that 2-month treatment with intraperitoneal injection of THC caused functional retinal impairment and increased apoptosis in photoreceptors by induction of inflammatory response and oxidative stress. Although the via of administration of THC was different from our study and retinal damage was detected directly in the exposed mice, these are evidences that the use of Cannabis induces an inflammatory state in the retina and it might be related to morphological changes [ 30 ]. In our study it is not possible to correlate the morphological changes in young adult and adult mice with functional retinal changes as the design of the study does not allow conclusions to be drawn in this regard.…”

Possible Role of Cannabis in the Management of Neuroinflammation in Patients with Post-COVID Condition

“…Additionally, in a retinal damage study, daily administration of THC (1 or 2 mg/kg) for two months induced a significant increase in oxidative stress, manifested by an increase in malondialdehyde (MDA) levels, a decrease in reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) activity and an increase in NOX-4 protein expression. In addition, there was an increase in nitric oxide, IL-1β, IL-6, and TNF-α production in mouse retina [108]. In a study on the pancreas, the effects of THC were investigated in rats with hyperinsulinemia.…”

Therapeutic Potential of Cannabinoids in Glaucoma

“…Contrary to the studies mentioned, some models also reported neurodysfunctional effects due to cannabinoids and their receptors. Two months of systemic treatment with Δ 9 -THC resulted in toxic effects on photoreceptor cells in mice through functional loss in electroretinography and apoptosis [ 148 ]. For a detailed overview of other studies on neuroprotection in ocular diseases, the reader is referred to more extensive reviews [ 9 , 20 , 60 ].…”