June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
microRNA Nanomedicines in Sjögren's Syndrome Dry Eye Disease
Author Affiliations & Notes
  • Sinéad Connolly
    Department of Ophthalmology, Royal College of Surgeons in Ireland, Dublin, Ireland
    Department of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland
  • Qistina Pilson
    Department of Ophthalmology, Royal Victoria Eye and Ear Hospital, Dublin, Ireland
  • Sally Ann Cryan
    School of Pharmacy, Royal College of Surgeons in Ireland, Dublin, Ireland
  • Joan Ni Gabhann
    Department of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland
    Department of Ophthalmology, Royal College of Surgeons in Ireland, Dublin, Ireland
  • Conor C Murphy
    Department of Ophthalmology, Royal College of Surgeons in Ireland, Dublin, Ireland
    Department of Ophthalmology, Royal Victoria Eye and Ear Hospital, Dublin, Ireland
  • Footnotes
    Commercial Relationships   Sinéad Connolly, None; Qistina Pilson, None; Sally Ann Cryan, None; Joan Ni Gabhann, None; Conor C Murphy, None
  • Footnotes
    Support  Irish College of Ophthalmology-Novartis Research Bursary 2016-2017. Royal Victoria Eye and Ear Hospital Research Foundation Funding Scheme 2015 & 2016
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 3922. doi:
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    • Get Citation

      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)

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Abstract

Purpose : 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.

Methods : 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.

Results : 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.

Conclusions : 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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