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Homer1a reduces inflammatory response after retinal ischemia/reperfusion injury
- Source :
- Neural Regeneration Research, Vol 19, Iss 7, Pp 1608-1617 (2024)
- Publication Year :
- 2024
- Publisher :
- Wolters Kluwer Medknow Publications, 2024.
-
Abstract
- 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.
Details
- Language :
- English
- ISSN :
- 16735374
- Volume :
- 19
- Issue :
- 7
- Database :
- Directory of Open Access Journals
- Journal :
- Neural Regeneration Research
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.18d3246fd7aa4608af0eda897e4fb092
- Document Type :
- article
- Full Text :
- https://doi.org/10.4103/1673-5374.386490