摘要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 Homer1flox/-/Homer1a+/-/Nestin-Cre+/-mice with elevated lOP-induced retinal ischemia/reperfusion injury.For in vitro experiments,the oxygen-glucose deprivation/reperfusion injury model was constructed with Muller cells.We found that Homer1a overexpression ameliorated the decreases in retinal thickness and Muller cell viability after ischemia/reperfusion injury.Furthermore,Homer1a knockdown promoted NF-κB P65Ser536 activation via caspase-8,NF-κB P65 nuclear translocation,NLRP3 inflammasome formation,and the production and processing of interleukin-1β 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 Homer1flox/-/Homer1a+/-/Nestin-Cre+/-mice and apoptosis in Muller cells after ischemia/reperfusion injury.Taken together,these studies demonstrate that Homer1a exerts protective effects on retinal tissue and Muller cells via the caspase-8/NF-κB P65/NLRP3 pathway after I/R injury.