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Pharmacol."],"abstract":"<jats:p>Caffeine, one of the most consumed central nervous system (CNS) stimulants, is an antagonist of A<jats:sub>1<\/jats:sub> and A<jats:sub>2A<\/jats:sub> adenosine receptors. In this study, we investigated the potential protective effects of this methylxanthine in the retinal tissue. We tested caffeine by using <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> 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-1\u03b2, IL-6, and TNF-\u03b1 and the nuclear translocation of p-NF\u03baB. 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 (<jats:italic>p<\/jats:italic> &amp;lt; 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.<\/jats:p>","DOI":"10.3389\/fphar.2021.824885","type":"journal-article","created":{"date-parts":[[2022,1,6]],"date-time":"2022-01-06T17:13:57Z","timestamp":1641489237000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":29,"title":["Caffeine Protects Against Retinal Inflammation"],"prefix":"10.3389","volume":"12","author":[{"given":"Federica","family":"Conti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Lazzara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni Luca","family":"Romano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara Bianca Maria","family":"Platania","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Drago","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Bucolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"81","DOI":"10.5409\/wjcp.v4.i4.81","article-title":"Caffeine Therapy in Preterm Infants","volume":"4","author":"Abdel-Hady","year":"2015","journal-title":"World J. 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