Neural Regeneration Research ›› 2024, Vol. 19 ›› Issue (7): 1608-1617.doi: 10.4103/1673-5374.386490

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Homer1a reduces inflammatory response after retinal ischemia/reperfusion injury

Yanan Dou1, #, Xiaowei Fei1, #, Xin He1, #, Yu Huan1, Jialiang Wei1, Xiuquan Wu1, Weihao Lyu1, Zhou Fei1, *, Xia Li1, *, Fei Fei2, *   

  1. 1Department of Neurosurgery, Xijing Hospital, Air Force Military Medical University, Xi’an, Shaanxi Province, China; 2Department of Ophthalmology, Xijing Hospital, Air Force Military Medical University, Xi’an, Shaanxi Province, China
  • Online:2024-07-15 Published:2023-11-28
  • Contact: Fei Fei, PhD, feeplus@163.com; Xia Li, PhD, lixia_fmmu@163.com; Zhou Fei, PhD, feizhou@fmmu.edu.cn.
  • Supported by:
    This study was supported by the Youth Development Project of Air Force Military Medical University, No. 21QNPY072; Key Project of Shaanxi Provincial Natural Science Basic Research Program, No. 2023-JC-ZD-48 (both to FF).

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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.

Key words: caspase-8, Homer1a, interleukin-18, interleukin-1β, intraocular pressure, ischemia/reperfusion injury, JSH-23, Müller cells, NLRP3, nuclear factor-kB p65, retina