Format

Send to

Choose Destination
Sci Rep. 2017 Dec 13;7(1):17527. doi: 10.1038/s41598-017-17869-y.

TRI Microspheres prevent key signs of dry eye disease in a murine, inflammatory model.

Author information

1
Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, 15261, USA.
2
Department of Chemical Engineering, University of Pittsburgh, Pittsburgh, PA, 15216, USA.
3
Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, 15261, USA. srlittle@pitt.edu.
4
Department of Chemical Engineering, University of Pittsburgh, Pittsburgh, PA, 15216, USA. srlittle@pitt.edu.
5
Department of Immunology, University of Pittsburgh, Pittsburgh, PA, 15213, USA. srlittle@pitt.edu.
6
Department of Ophthalmology, University of Pittsburgh, Pittsburgh, PA, 15213, USA. srlittle@pitt.edu.
7
Department of Pharmaceutical Science, University of Pittsburgh, Pittsburgh, PA, 15261, USA. srlittle@pitt.edu.

Abstract

Dry eye disease (DED) is a highly prevalent, ocular disorder characterized by an abnormal tear film and ocular surface. Recent experimental data has suggested that the underlying pathology of DED involves inflammation of the lacrimal functional unit (LFU), comprising the cornea, conjunctiva, lacrimal gland and interconnecting innervation. This inflammation of the LFU ultimately results in tissue deterioration and the symptoms of DED. Moreover, an increase of pathogenic lymphocyte infiltration and the secretion of pro-inflammatory cytokines are involved in the propagation of DED-associated inflammation. Studies have demonstrated that the adoptive transfer of regulatory T cells (Tregs) can mediate the inflammation caused by pathogenic lymphocytes. Thus, as an approach to treating the inflammation associated with DED, we hypothesized that it was possible to enrich the body's own endogenous Tregs by locally delivering a specific combination of Treg inducing factors through degradable polymer microspheres (TRI microspheres; TGF-β1, Rapamycin (Rapa), and IL-2). This local controlled release system is capable of shifting the balance of Treg/T effectors and, in turn, preventing key signs of dry eye disease such as aqueous tear secretion, conjunctival goblet cells, epithelial corneal integrity, and reduce the pro-inflammatory cytokine milieu in the tissue.

PMID:
29235530
PMCID:
PMC5727478
DOI:
10.1038/s41598-017-17869-y
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center