Purchase this article with an account.
Shimon Ben-Shabat, Shiela Hauzner, Mor Cohen, Elie Beit-Yannai; Protective role of the cannabinoid receptor system in A2E-mediated photo-toxicity to retinal pigment epithelium (RPE) cells in an in-vitro model of age-related macular degeneration (AMD). Invest. Ophthalmol. Vis. Sci. 2014;55(13):617.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Accumulation in the RPE of A2E, a pyridinium bis-retinoid, has the potential to cause RPE cell death and may contribute to the RPE cell atrophy that is observed in AMD. The cannabinoid receptor system is present in human RPE cells and is intimately involved in the oxidative damage process, including that associated with AMD. It has been shown that levels of endocannabinoids are significantly increased in retinal tissue from AMD donors. This study aimed to investigate the effects of pro-inflammatory agents and specific oxidative intracellular signalling related proteins- MAPKs, on the in vitro AMD-A2E model in the presence and absence of cannabinoids (HU-210 and HU-308) and endocannabinoids (anandamide and 2-Ara-Gl)).
By using A2E-loaded RPE cells exposed to blue light irradiation, we can mimic the oxidative stress taking place in AMD. The presence of pro-inflammatory agents and activation of the signalling pathway were assessed in the presence and absence of cannabinoids and endocannabinoids by using Western-blot analysis, flow-cytometry and ELISA.
Experiments were conducted to investigate the ability of cannabinoids to attenuate the effect of A2E on the pro-inflammation agent's secretion. When the RPE cells were exposed to A2E and blue light, anandamide successfully and significantly reduced the amount of the pro-inflammatory chemokine, IL-8. The selective CB1 and CB2 receptor agonists, HU-210 and HU-308, respectively, did not influence IL-8 secretion. A2E alone caused an increase in IL-8 secretion that was attenuated by both HU-210 and HU-308. The ability of irradiated A2E-loaded RPE cells to induce MAPKs pathway activation was also evaluated. A significant decrease in several signals of MAPK was determined following RPE exposure to A2E and blue light irradiation, especially by HU-210 and HU-308.
The above results support our hypothesis that the newly discovered cannabinoid receptor system may attenuate AMD generated by the accumulation of A2E. This study is expected to select candidate therapeutic compounds that may contribute to delaying or arresting A2E-related toxicity to the RPE.
This PDF is available to Subscribers Only