Saraswathy Sindhu, Rao Narsing A
Department of Ophthalmology, Doheny Eye Institute, Los Angeles, CA, United States.
Department of Opthalmology, USC-Roski Eye Institute, University of Southern California, Los Angeles, CA, United States.
Front Ophthalmol (Lausanne). 2023 Mar 24;3:1130202. doi: 10.3389/fopht.2023.1130202. eCollection 2023.
Uveitis and related intraocular inflammations are a major cause of blindness due to retinal damage caused by degeneration and loss of the photoreceptor cells. In mouse experimental autoimmune uveitis (EAU) previously we have shown mitochondrial oxidative stress with marked upregulation of αA crystallin in the inner segments of the photoreceptors. Furthermore, αA crystallin treatment prevented photoreceptor mitochondrial oxidative stress by suppressing innate and adaptive immunity in EAU.
Since these immune processes are modulated by microRNAs, in this study we investigated (a) modulation of microRNAs during development of EAU by αA crystallin administration and (b) microRNA therapeutic intervention.
Few microRNAs were significantly upregulated in EAU mice with intravenous injection of αA crystallin and among these, computational bioinformatic analysis revealed that the upregulated microRNA 146a targets the innate and adaptive immune responses. In EAU, intravenous as well as intravitreal administration of this microRNA prevented inflammatory cell infiltration in uvea and retina and preserved photoreceptor cells.
This protective function suggests that microRNA146a can be a novel therapeutic agent in preventing retinal damage in uveitis.
葡萄膜炎及相关眼内炎症是导致失明的主要原因，这是由光感受器细胞变性和丧失所引起的视网膜损伤所致。在小鼠实验性自身免疫性葡萄膜炎（EAU）中，我们之前已经表明，光感受器内节存在线粒体氧化应激，且αA晶状体蛋白显著上调。此外，αA晶状体蛋白治疗通过抑制EAU中的先天性和适应性免疫，预防了光感受器线粒体氧化应激。
由于这些免疫过程受微小RNA调控，在本研究中，我们调查了（a）通过给予αA晶状体蛋白在EAU发展过程中微小RNA的调控情况，以及（b）微小RNA治疗干预。
静脉注射αA晶状体蛋白的EAU小鼠中，少数微小RNA显著上调，其中，通过计算生物信息学分析发现，上调的微小RNA 146a靶向先天性和适应性免疫反应。在EAU中，静脉注射以及玻璃体内注射这种微小RNA可预防葡萄膜和视网膜中的炎性细胞浸润，并保留光感受器细胞。
这种保护作用表明，微小RNA146a可能是预防葡萄膜炎中视网膜损伤的新型治疗药物。
