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<p>Retinal ischemia-reperfusion (RIR) injury is a common pathophysiological phenomenon in retinal ischemic diseases, leading to neuronal damage of the retina and irreversible vision impairment. However, the mechanisms underlying neuronal damage in RIR are complex and remain incompletely understood. In this study, the critical role of the signal transducer and activator of transcription 3 (STAT3) in RIR pathology and its contribution to RIPK1-mediated PANoptosome assembly, thereby inducing PANoptosis in the retina, were identified. Consequently, a thermosensitive nanocarrier-drug system (ASX-NP), integrating astaxanthin (ASX) polymer with the STAT3 inhibitor Stattic, was successfully designed and synthesized <i>via</i> ultrasonic emulsification. The protective effects of ASX-NP on retinal ganglion cells (RGCs) and optic nerve were evaluated. ASX-NP significantly decreased RGCs loss and restored visual function in RIR model mice, with protective effects primarily attributed to the inhibition of STAT3-RIPK1-PANoptosis signal axis, as well as exerting anti-inflammatory and antioxidant effects in retinal cells. Overall, ASX-NP shows encouraging antioxidant and neuroprotective properties in RIR, indicating its potential for future clinical applications. This current study, therefore, reveals a complete signaling pathway that regulates the PANoptosome to PANoptosis and provides a promising nanomedicine-based therapeutic strategy for a wide range of retinal diseases underpinned by RIR pathology.</p>

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Thermo-responsive astaxanthin-polymeric nanocarriers targeting STAT3-RIPK1 mediated PANoptosome formation for neuroprotection in retinal injury

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月20日

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  • Rong Rong,
  • Jiamiao Liu,
  • Ganghao Liang,
  • Yixian Liu,
  • Xiaobo Xia

摘要

Retinal ischemia-reperfusion (RIR) injury is a common pathophysiological phenomenon in retinal ischemic diseases, leading to neuronal damage of the retina and irreversible vision impairment. However, the mechanisms underlying neuronal damage in RIR are complex and remain incompletely understood. In this study, the critical role of the signal transducer and activator of transcription 3 (STAT3) in RIR pathology and its contribution to RIPK1-mediated PANoptosome assembly, thereby inducing PANoptosis in the retina, were identified. Consequently, a thermosensitive nanocarrier-drug system (ASX-NP), integrating astaxanthin (ASX) polymer with the STAT3 inhibitor Stattic, was successfully designed and synthesized via ultrasonic emulsification. The protective effects of ASX-NP on retinal ganglion cells (RGCs) and optic nerve were evaluated. ASX-NP significantly decreased RGCs loss and restored visual function in RIR model mice, with protective effects primarily attributed to the inhibition of STAT3-RIPK1-PANoptosis signal axis, as well as exerting anti-inflammatory and antioxidant effects in retinal cells. Overall, ASX-NP shows encouraging antioxidant and neuroprotective properties in RIR, indicating its potential for future clinical applications. This current study, therefore, reveals a complete signaling pathway that regulates the PANoptosome to PANoptosis and provides a promising nanomedicine-based therapeutic strategy for a wide range of retinal diseases underpinned by RIR pathology.