Cheng Zhang, Lemeng Feng, Weiming Zhu, Min He, Chao Wang, Ye He, Wulong Zhang, Jiayi Li, Haoze Song, Weitao Song
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Regulation of Retinal Microglia by Framework Nucleic Acid-Mediated Delivery of microRNA-124 Protects Retinal Ganglion Cells in Acute Glaucoma.
Glaucoma is a leading cause of irreversible blindness, characterized by the progressive degeneration of retinal ganglion cells (RGCs) and optic nerve damage. Although current intraocular pressure (IOP)-lowering therapies exhibit varying degrees of efficacy in preventing RGC loss, neurodegeneration can persist even in cases where IOP remains within the normal range, underscoring the need for direct neuroprotective strategies. Emerging evidence suggests that neuroinflammation mediated by retinal microglia plays a pivotal role in the pathogenesis of glaucoma. Here, a nucleic acid-based nanotherapeutic platform is proposed that employs tetrahedral framework nucleic acids (tFNAs) conjugated with microRNA-124 (miR-124), referred to as Tmi, to achieve targeted immunomodulation. Compared with conventional delivery systems, this self-assembled nanostructure exhibits superior cellular penetration and nucleic acid protection capabilities. Mechanistic studies demonstrate that Tmi-mediated inhibition of the STAT3 pathway attenuates excessive microglial activation, reduces migration-associated inflammation, and suppresses pathological cell migration in an acute ocular hypertension model. This is an alternative treatment strategy beyond intraocular pressure control, offering greater possibilities for exploring therapies for acute high intraocular pressure glaucoma.
期刊介绍:
Advanced Healthcare Materials, a distinguished member of the esteemed Advanced portfolio, has been dedicated to disseminating cutting-edge research on materials, devices, and technologies for enhancing human well-being for over ten years. As a comprehensive journal, it encompasses a wide range of disciplines such as biomaterials, biointerfaces, nanomedicine and nanotechnology, tissue engineering, and regenerative medicine.