Zhao Yi-Ming, Sun Rong-Sha, Duan Fang, Wang Fang-Yu, Li Yu-Jie, Qian Xiao-Bing, Zeng Jie-Ting, Yang Yao, Lin Xiao-Feng
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, Guangdong Province, China.
Xi'an People's Hospital (Xi'an Fourth Hospital), Shaanxi Eye Hospital, Xi'an 710004, Shaanxi Province, China.
Int J Ophthalmol. 2023 Jan 18;16(1):22-32. doi: 10.18240/ijo.2023.01.04. eCollection 2023.
To evaluate the effects of intravitreal slow-release dexamethasone on traumatic proliferative vitreoretinopathy (PVR) and Müller cell gliosis and preliminarily explored the possible inflammatory mechanism in a rabbit model induced by penetrating ocular trauma.
Traumatic PVR was induced in the right eyes of pigmented rabbits by performing an 8-mm circumferential scleral incision placed 2.5 mm behind the limbus, followed by treatment with a slow-release dexamethasone implant (Ozurdex) or sham injection. Left eyes were used as normal controls. The intraocular pressure (IOP) was monitored using an iCare tonometer. PVR severity was evaluated anatomical and histopathological examinations every week for 6wk; specific inflammatory cytokine and proliferative marker levels were measured by quantitative real-time polymerase chain reaction, Western blot, protein chip analysis, or immunofluorescence staining.
During the observation period, PVR severity gradually increased. Intense Müller cell gliosis was observed in the peripheral retina near the wound and in the whole retina of PVR group. Ozurdex significantly alleviated PVR development and Müller cell gliosis. Post-traumatic inflammation fluctuated and was persistent. The interleukin-1β (IL-1β) mRNA level was significantly upregulated, peaking on day 3 and increasing again on day 21 after injury. The expression of nod-like receptor family pyrin domain containing 3 (NLRP3) showed a similar trend that began earlier than that of IL-1β expression. Ozurdex suppressed the expression of IL-1β, NLRP3, and phosphorylated nuclear factor-kappa B (NF-κB). The average IOP after treatment was within normal limits.
The present study demonstrates chronic and fluctuating inflammation in a traumatic PVR rabbit model over 6wk. Ozurdex treatment significantly inhibites inflammatory cytokines expression and Müller cell gliosis, and thus alleviates PVR severity. This study highlights the important role of IL-1β, and Ozurdex inhibites inflammation presumably the NF-κB/NLRP3/IL-1β inflammatory axis. In summary, Ozurdex provides a potential therapeutic option for traumatic PVR.
评估玻璃体内缓释地塞米松对创伤性增殖性玻璃体视网膜病变（PVR）和 Müller 细胞胶质化的影响，并在穿透性眼外伤诱导的兔模型中初步探讨其可能的炎症机制。
通过在色素兔右眼角膜缘后 2.5 mm 处进行 8 mm 环形巩膜切开术诱导创伤性 PVR，随后用缓释地塞米松植入物（Ozurdex）治疗或假注射。左眼用作正常对照。使用 iCare 眼压计监测眼压。每周进行 6 周的解剖和组织病理学检查以评估 PVR 严重程度；通过定量实时聚合酶链反应、蛋白质印迹、蛋白质芯片分析或免疫荧光染色测量特定炎症细胞因子和增殖标志物水平。
在观察期内，PVR 严重程度逐渐增加。在伤口附近的周边视网膜和 PVR 组的整个视网膜中观察到强烈的 Müller 细胞胶质化。Ozurdex 显著减轻了 PVR 的发展和 Müller 细胞胶质化。创伤后炎症波动且持续存在。白细胞介素-1β（IL-1β）mRNA 水平显著上调，在损伤后第 3 天达到峰值，并在第 21 天再次升高。含吡喃结构域的 NOD 样受体家族 3（NLRP3）的表达呈现类似趋势，且比 IL-1β 表达开始得更早。Ozurdex 抑制了 IL-1β、NLRP3 和磷酸化核因子-κB（NF-κB）的表达。治疗后的平均眼压在正常范围内。
本研究证明了创伤性 PVR 兔模型在 6 周内存在慢性和波动性炎症。Ozurdex 治疗显著抑制炎症细胞因子表达和 Müller 细胞胶质化，从而减轻 PVR 严重程度。本研究突出了 IL-1β 的重要作用，并且 Ozurdex 可能通过 NF-κB/NLRP3/IL-1β 炎症轴抑制炎症。总之，Ozurdex 为创伤性 PVR 提供了一种潜在的治疗选择。
