The pathogenesis of outer retinal degenerations has been linked to the elevation of cytokines that orchestrate pro-inflammatory responses within the retinal milieu, and which are thought to play a role in diseases such as geographic atrophy (GA), an advanced form of AMD. Here we sought investigate the anti-inflammatory and mechanistic properties of fludrocortisone (FA), as well as triamcinolone acetonide (TA), on Müller cell-mediated cytokine expression in response to inflammatory challenge. In addition, we investigated the neuroprotective efficacy of FA and TA in a photo-oxidative damage (PD), a model of outer retinal degeneration. Expression of CCL2, IL-6, and IL-8 with respect to FA and TA were assessed in Müller cells in vitro, following simulation with IL-1β or TNF-α. The dependency of this effect on mineralocorticoid and glucocorticoid signaling was also interrogated for both TA and TA via co-incubation with steroid receptor antagonists. For the PD model, C57BL/6 mice were intravitreally injected with FA or TA, and changes in retinal pathology were assessed via electroretinogram (ERG) and optical coherence tomography (OCT). FA and TA were found to dramatically reduce the expression of CCL2, IL-6, and IL-8 in Müller glia in vitro after inflammatory challenge with IL-1β or TNF-α (P < 0.05). Though FA acts as both a mineralocorticoid and glucocorticoid receptor agonist, co-incubation with selective steroid antagonists revealed that the suppressive effect of FA on CCL2, IL-6, and IL-8 expression is mediated by glucocorticoid signaling (P < 0.05). In PD, intravitreal FA was found to ameliorate outer-retinal atrophy as measured by ERG and OCT (P < 0.05), while TA had no significant effect (P > 0.05). Our data indicate potent anti-inflammatory and mechanistic properties of corticosteroids, specifically FA, in suppressing inflammation and neurodegeneration degeneration associated with outer retinal atrophy. Taken together, our findings indicate that corticosteroids such as FA may have value as a potential therapeutic for outer retinal degenerations where such pro-inflammatory factors are implicated, including AMD.

外层视网膜变性的发病机制与细胞因子的升高有关，这些细胞因子在视网膜环境中协调促炎反应，并且被认为在诸如地理萎缩 (GA) 等疾病中起作用，这是一种高级形式的 AMD。在这里，我们寻求研究氟氢可的松 (FA) 以及曲安奈德 (TA) 对 Müller 细胞介导的细胞因子表达以响应炎症挑战的抗炎和机械特性。此外，我们研究了 FA 和 TA 在光氧化损伤 (PD)（一种外层视网膜变性模型）中的神经保护功效。的表达CCL2，IL-6，和IL-8在Müller细胞进行了评估相对于FA和TA体外，在用 IL-1β 或 TNF-α 模拟之后。这种作用对盐皮质激素和糖皮质激素信号传导的依赖性也通过与类固醇受体拮抗剂的共同孵育对 TA 和 TA 进行了询问。对于 PD 模型，C57BL/6 小鼠玻璃体内注射 FA 或 TA，并通过视网膜电图 (ERG) 和光学相干断层扫描 (OCT) 评估视网膜病理学的变化。发现 FA 和 TA在用 IL-1β 或 TNF-α 炎症攻击后显着降低体外Müller 胶质细胞中CCL2、IL-6和IL-8的表达（P < 0.05）。虽然 FA 既是盐皮质激素又是糖皮质激素受体激动剂，但与选择性类固醇拮抗剂共同孵育表明 FA 对CCL2、IL-6和IL-8表达由糖皮质激素信号介导（P < 0.05）。在 PD 中，通过 ERG 和 OCT 测量发现玻璃体内 FA 可改善外视网膜萎缩（P < 0.05），而 TA 没有显着影响（P > 0.05）。我们的数据表明皮质类固醇（特别是 FA）在抑制与外层视网膜萎缩相关的炎症和神经变性退化方面具有强大的抗炎和机械特性。综上所述，我们的研究结果表明，皮质类固醇（如 FA）可能具有潜在治疗外视网膜变性的价值，其中涉及此类促炎因子，包括 AMD。