Caffeine administration prevents retinal neuroinflammation and loss of retinal ganglion cells in an animal model of glaucoma

Abstract

Glaucoma is the second leading cause of blindness worldwide, being characterized by progressive optic nerve damage and loss of retinal ganglion cells (RGCs), accompanied by increased inflammatory response involving retinal microglial cells. The etiology of glaucoma is still unknown, and despite elevated intraocular pressure (IOP) being a major risk factor, the exact mechanisms responsible for RGC degeneration remain unknown. Caffeine, which is an antagonist of adenosine receptors, is the most widely consumed psychoactive drug in the world. Several evidences suggest that caffeine can attenuate the neuroinflammatory responses and afford protection upon central nervous system (CNS) injury. We took advantage of a well characterized animal model of glaucoma to investigate whether caffeine administration controls neuroinflammation and elicits neuroprotection. Caffeine or water were administered ad libitum and ocular hypertension (OHT) was induced by laser photocoagulation of the limbal veins in Sprague Dawley rats. Herein, we show that caffeine is able to partially decrease the IOP in ocular hypertensive animals. More importantly, we found that drinking caffeine prevented retinal microglia-mediated neuroinflammatory response and attenuated the loss of RGCs in animals with ocular hypertension (OHT). This study opens the possibility that caffeine or adenosine receptor antagonists might be a therapeutic option to manage RGC loss in glaucoma.

Blockade of microglial adenosine A2A receptor suppresses elevated pressure‐induced inflammation, oxidative stress, and cell death in retinal cells

“…Modeling ocular hypertension in vitro increased the expression of TSPO and MHC‐II in retinal neural cells, consistent with a response of microglia to elevated pressure. Also, A 2A R antagonist prevented this increase, suggesting that microglial A 2A R controls neuroinflammation, as has been suggested previously (Boia et al, ; Madeira et al, ).…”

Health status and productivity of sheep fed coffee pulp during fattening

“…Coffee pulp contains caffeine (Salinas et al 2014), which is widely used for its different physiological effects. For example, caffeine is used in children with apnea as an inhibitor of adenosine receptors and as a modulator of inflammatory processes to decrease the quantity of neutrophils by inhibiting IL-10 (Chavez et al 2011) and TNF-α expression (Horrigan et al 2004), and in laboratory animals as an anti-inflammatory factor for the prevention of glaucoma (Madeira et al 2016). Li et al (2011) observed that caffeine decreased the chemotaxis and phagocytic activity of neutrophils in pig spermatozoa.…”

Caveolin-1–mediated internalization of the vitamin C transporter SVCT2 in microglia triggers an inflammatory phenotype

“…2H). Finally, stimulating microglial activation and inflammation in the rat retina in vivo by intravitreous injection of LPS or performing retinal ischemia-reperfusion injury (36)(37)(38)(39)(40) reduced SVCT2 abundance in the retina (Fig. 2, I and J).…”