Homer1a reduces inflammatory response after retinal ischemia/reperfusion injury.

Abstract

Abstract JOURNAL/nrgr/04.03/01300535-202407000-00042/figure1/v/2023-11-20T171125Z/r/image-tiff 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 IOP-induced retinal ischemia/reperfusion injury. For in vitro experiments, the oxygen-glucose deprivation/reperfusion injury model was constructed with Müller cells. We found that Homer1a overexpression ameliorated the decreases in retinal thickness and Müller 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 Müller cells after ischemia/reperfusion injury. Taken together, these studies demonstrate that Homer1a exerts protective effects on retinal tissue and Müller cells via the caspase-8/NF-κB P65/NLRP3 pathway after I/R injury.