Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang University, Seoul 04763, Republic of Korea.
Department of Internal Medicine, Yale University, New Haven, CT 06520, USA.
Cells. 2024 Mar 20;13(6):548. doi: 10.3390/cells13060548.
Age-related macular degeneration (AMD), characterized by macular retinal degeneration, poses a significant health concern due to the lack of effective treatments for prevalent dry AMD. The progression of AMD is closely linked to reactive oxygen species and Fas signaling, emphasizing the need for targeted interventions. In this study, we utilized a NaIO-induced retinal degeneration mouse model to assess the efficacy of Fas-blocking peptide (FBP). Intravitreal administration of FBP successfully suppressed Fas-mediated inflammation and apoptosis, effectively arresting AMD progression in mice. We developed a 6R-conjugated FBP (6R-FBP) for eye drop administration. 6R-FBP, administered as an eye drop, reached the retinal region, attenuating degeneration by modulating the expression of inflammatory cytokines and blocking Fas-mediated apoptosis in rodent and rabbit NaIO-induced retinal degeneration models to address practical concerns. Intravitreal FBP and 6R-FBP eye drops effectively reduced retinal degeneration and improved retinal thickness in rodent and rabbit models. This study highlights the therapeutic potential of FBP, particularly 6R-FBP as an eye drop, in inhibiting Fas-mediated cell signaling and protecting against retinal cell death and inflammation in dry AMD. Future investigations should explore the translational prospects of this approach in primates with eye structures comparable to those of humans.
年龄相关性黄斑变性（AMD），以黄斑视网膜变性为特征，由于缺乏对常见干性 AMD 的有效治疗方法，因此成为一个重大的健康关注点。AMD 的进展与活性氧和 Fas 信号密切相关，这强调了需要进行有针对性的干预。在这项研究中，我们使用了 NaIO 诱导的视网膜变性小鼠模型来评估 Fas 阻断肽（FBP）的疗效。玻璃体内给予 FBP 成功抑制了 Fas 介导的炎症和细胞凋亡，有效阻止了小鼠 AMD 的进展。我们开发了一种 6R 缀合的 FBP（6R-FBP）用于滴眼。6R-FBP 作为滴眼剂给药，到达视网膜区域，通过调节炎症细胞因子的表达并阻断 Fas 介导的细胞凋亡，减轻了 rodent 和兔 NaIO 诱导的视网膜变性模型中的变性，解决了实际问题。玻璃体内 FBP 和 6R-FBP 滴眼剂有效减轻了 rodent 和兔模型中的视网膜变性并改善了视网膜厚度。这项研究强调了 FBP，特别是作为滴眼剂的 6R-FBP，在抑制 Fas 介导的细胞信号传导以及保护干性 AMD 中的视网膜细胞死亡和炎症方面的治疗潜力。未来的研究应探索该方法在与人类眼睛结构相似的灵长类动物中的转化前景。
