Homer1a reduces inflammatory response after retinal ischemia/reperfusion injury

Elevated intraocular pressure (IOP) is one of the causes of retinal ischemia/reperfusion injury, which results in NLRP3 inflammasome activation and leads to visual damage. Homer1a is reported to play a protective role in neuroinflammation in the cerebrum. However, the effects of Homer1a on NLRP3 inflammasomes in retinal ischemia/reperfusion injury caused by elevated IOP remain unknown. In our study, animal models were constructed using C57BL/6J and Homer1(flox/)(-)/Homer1a(+/)(-)/Nestin-Cre(+/)(-) mice with elevated IOP-induced retinal ischemia/reperfusion injury. For in vitro experiments, the oxygen-glucose deprivation/reperfusion injury model was constructed with M & uuml;ller cells. We found that Homer1a overexpression ameliorated the decreases in retinal thickness and M & uuml;ller cell viability after ischemia/reperfusion injury. Furthermore, Homer1a knockdown promoted NF-kappa B P65(Ser536) activation via caspase-8, NF-kappa B P65 nuclear translocation, NLRP3 inflammasome formation, and the production and processing of interleukin-1 beta and interleukin-18. The opposite results were observed with Homer1a overexpression. Finally, the combined administration of Homer1a protein and JSH-23 significantly inhibited the reduction in retinal thickness in Homer1(flox/)(-)/Homer1a(+/)(-)/Nestin-Cre(+/)(-) mice and apoptosis in M & uuml;ller cells after ischemia/reperfusion injury. Taken together, these studies demonstrate that Homer1a exerts protective effects on retinal tissue and M & uuml;ller cells via the caspase-8/NF-kappa B P65/NLRP3 pathway after I/R injury.