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Sinéad Connolly, Qistina Pilson, Sally Ann Cryan, Joan Ni Gabhann, Conor C Murphy; microRNA Nanomedicines in Sjögren's Syndrome Dry Eye Disease. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3922.
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© ARVO (1962-2015); The Authors (2016-present)
Primary Sjögren’s syndrome (pSS) is a disorder characterised by autoimmune destruction of exocrine glands, leading to the sicca complex of dry eyes and dry mouth. The exact aetopathogenesis remains obscure, however a signature of Type 1 interferons and proinflammatory cytokines is strongly associated with pSS. miRNAs) are endogenous small RNAs which act on messenger RNA at a post-transcriptional level. There is a growing understanding that altered expression of miRNA is involved in the pSS phenotype, and may promote inflammation in pSS by increasing cytokine production.Modulation of miRNA presents a potential new treatment paradigm for pSS dry eye, but effective and safe methods of delivery to the ocular surface limit clinical translation. Polymeric nanoparticles were investigated for delivery of miRNA modulating compounds to the ocular surface. Anti-sense RNA to miR-744-5p cargo, a miRNA overexpressed in conjunctival epithelial cells of pSS patients, was used to determine efficiency.
Chitosan polymers were used to prepare miRNA nanomedicines, characterised for their size, surface (zeta) potential, RNA complexation efficiency, and screened for transfection efficiency and toxicity in IMCEC Human Conjunctival Epithelial Cells. Manufacture was optimised to obtain small particles which effectively complex miRNA at a variety of NP ratios.
Average hydrodynamic diameter of chitosan nanoparticles was 207 nm with a narrow size distribution. The nanoparticles also possessed positive surface charges up to +25 mV in water, thus enabling effective condensation of negatively charged microRNA.Cells treated with chitosan nanoparticles showed decreased expression of miR-744-5p and increased expression of Pellino 3 mRNA.
An optimised microRNA nanoparticle delivery system has therapeutic potential for modulating inflammation at the ocular surface.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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