Abstract
Caffeine, one of the most consumed central nervous system (CNS) stimulants, is an antagonist of A1 and A2A adenosine receptors. In this study, we investigated the potential protective effects of this methylxanthine in the retinal tissue. We tested caffeine by using in vitro and in vivo paradigms of retinal inflammation. Human retinal pigment epithelial cells (ARPE-19) were exposed to lipopolysaccharide (LPS) with or without caffeine. This latter was able to reduce the inflammatory response in ARPE-19 cells exposed to LPS, attenuating the release of IL-1β, IL-6, and TNF-α and the nuclear translocation of p-NFκB. Additionally, caffeine treatment restored the integrity of the ARPE-19 monolayer assessed by transepithelial electrical resistance (TEER) and the sodium fluorescein permeability test. Finally, the ischemia reperfusion (I/R) injury model was used in C57BL/6J mice to induce retinal inflammation and investigate the effects of caffeine treatment. Mouse eyes were treated topically with caffeine, and a pattern electroretinogram (PERG) was used to assess the retinal ganglion cell (RGC) function; furthermore, we evaluated the levels of IL-6 and BDNF in the retina. Retinal BDNF dropped significantly (p < 0.05) in the I/R group compared to the control group (normal mice); on the contrary, caffeine treatment maintained physiological levels of BDNF in the retina of I/R eyes. Caffeine was also able to reduce IL-6 mRNA levels in the retina of I/R eyes. In conclusion, these findings suggest that caffeine is a good candidate to counteract inflammation in retinal diseases.
Highlights
Caffeine is the 1,3,7 trimethylxanthine and represents one of the most consumed central nervous system (CNS) stimulants, with an average assumption within 100–400 mg per day (Sc and Muralidhara, 2016), through consumption of coffee, tea, and soft drinks enriched with caffeine (Mitchell et al, 2014), along with caffeine supplements, generally used as metabolism boosters (Gurley et al, 2015)
Caffeine is a non-selective adenosine receptor (AR) antagonist, it has a higher affinity for the adenosine A1 receptor (A1R) and the adenosine A2A receptor (A2AR); caffeine is a non-selective inhibitor of phosphodiesterases (PDEs)
We found that caffeine upregulated the BDNF expression in ARPE-19 cells exposed to LPS, even though the intermediate concentration (10 μM) did not have effect (Figure 2D)
Summary
Caffeine is the 1,3,7 trimethylxanthine and represents one of the most consumed central nervous system (CNS) stimulants, with an average assumption within 100–400 mg per day (Sc and Muralidhara, 2016), through consumption of coffee, tea, and soft drinks enriched with caffeine (Mitchell et al, 2014), along with caffeine supplements, generally used as metabolism boosters (Gurley et al, 2015). A1R and A2AR are G-protein–coupled receptors (GPCRs), and they are expressed in human retinal pigment epithelial (RPE) cells (Wan et al, 2011) and in other layers of the retina (Fredholm et al, 2011; Wurm et al, 2011; Liu et al, 2018). The retinal inflammatory process occurs in several ocular diseases such as age-related macular degeneration (AMD) and diabetic retinopathy (DR). This latter is one of the leading causes of irreversible vision loss in industrialized countries and represents a severe retinal degenerative disease (Van Lookeren Campagne et al, 2014). The aim of the present study was to explore the neuroprotective and the anti-inflammatory effects of caffeine in two models of retinal inflammation by using human RPE cells and C57BL/6J mice, respectively
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