Published paper results from 2018 ORIA funding. MicroRNA-223 Regulates Retinal Function and Inflammation in the Healthy and Degenerating Retina
We are pleased our members and grant recipients contact us regularly about their work. We would like to congratulations to Nilisha Fernando and their team who have published papers as a result of the @oria_au funding. Click on the link below for the whole paper.
MicroRNA-223 Regulates Retinal Function and Inflammation in the Healthy and Degenerating Retina
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.
Nilisha Fernando1, Josephine H. C. Wong1, Shannon Das1, Catherine Dietrich1,
Riemke Aggio-Bruce1,2, Adrian V. Cioanca1, Yvette Wooff1,2, Joshua A. Chu-Tan1,2,
Ulrike Schumann1, Chinh Ngo1, Rohan W. Essex3, Camilla Dorian4, Sarah A. Robertson4, Si Ming Man1, Jan Provis1 and Riccardo Natoli1,2*