Academic Journal

MicroRNA-223 regulates retinal function and inflammation in the healthy and degenerating retina

التفاصيل البيبلوغرافية
العنوان: MicroRNA-223 regulates retinal function and inflammation in the healthy and degenerating retina
المؤلفون: Fernando, N., Wong, J.H.C., Das, S., Dietrich, C., Aggio-Bruce, R., Cioanca, A.V., Wooff, Y., Chu-Tan, J.A., Schumann, U., Ngo, C., Essex, R.W., Dorian, C., Robertson, S.A., Man, S.M., Provis, J., Natoli, R.
المصدر: http://dx.doi.org/10.3389/fcell.2020.00516.
بيانات النشر: Frontiers Media
سنة النشر: 2020
المجموعة: The University of Adelaide: Digital Library
مصطلحات موضوعية: macrophage, microRNA, microRNA-223, microglia, neuroinflammation, photoreceptor cell death, retinal degeneration, retinal function
الوصف: Introduction:MicroRNAs (miRNAs) are small, non-coding RNA molecules that have powerful regulatory properties, with the ability to regulate multiple messenger RNAs (mRNAs) and biological pathways. MicroRNA-223-3p (miR-223) is known to be a critical regulator of the innate immune response, and its dysregulation is thought to play a role in inflammatory disease progression. Despite miR-223 upregulation in numerous neurodegenerative conditions, largely in cells of the myeloid lineage, the role of miR-223 in the retina is relatively unexplored. Here, we investigated miR-223 in the healthy retina and in response to retinal degeneration. Methods:miR-223-null mice were investigated in control and photo-oxidative damage-induced degeneration conditions. Encapsulated miR-223 mimics were intravitreally and intravenously injected into C57BL/6J wild-type mice. Retinal functional responses were measured using electroretinography (ERG), while extracted retinas were investigated by retinal histology (TUNEL and immunohistochemistry) and molecular analysis (qPCR and FACS). Results:Retinal function in miR-223-/- mice was adversely affected, indicating that miR-223 may be critical in regulating the retinal response. In degeneration, miR-223 was elevated in the retina, circulating serum, and retinal extracellular vesicles. Conversely, retinal microglia and macrophages displayed a downregulation of miR-223. Further, isolated CD11b+ inflammatory cells from the retinas and circulation of miR-223-null mice showed an upregulation of pro-inflammatory genes that are critically linked to retinal inflammation and progressive photoreceptor loss. Finally, both local and systemic delivery of miR-223 mimics improved retinal function in mice undergoing retinal degeneration. Conclusion:miR-223 is required for maintaining normal retinal function, as well as regulating inflammation in microglia and macrophages. Further investigations are required to determine the targets of miR-223 and their key biological pathways and interactions that are relevant ...
نوع الوثيقة: article in journal/newspaper
اللغة: English
تدمد: 2296-634X
Relation: http://purl.org/au-research/grants/nhmrc/1127705; Frontiers in Cell and Developmental Biology, 2020; 8:516-516; http://hdl.handle.net/2440/127257; Robertson, S.A. [0000-0002-9967-0084]
DOI: 10.3389/fcell.2020.00516
الاتاحة: http://hdl.handle.net/2440/127257
https://doi.org/10.3389/fcell.2020.00516
Rights: © 2020 Fernando, Wong, Das, Dietrich, Aggio-Bruce, Cioanca, Wooff, Chu-Tan, Schumann, Ngo, Essex, Dorian, Robertson, Man, Provis and Natoli. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
رقم الانضمام: edsbas.6AC9C831
قاعدة البيانات: BASE
الوصف
تدمد:2296634X
DOI:10.3389/fcell.2020.00516