TY - JOUR
T1 - TRI Microspheres prevent key signs of dry eye disease in a murine, inflammatory model
AU - Ratay, Michelle L.
AU - Balmert, Stephen C.
AU - Acharya, Abhinav P.
AU - Greene, Ashlee C.
AU - Meyyappan, Thiagarajan
AU - Little, Steven R.
N1 - Funding Information:
This work was supported in part by the National Institutes of Health (NIH) CORE Grant P30 EY008098, the University of Pittsburgh, Pittsburgh, PA; an unrestricted grant from Research to Prevent Blindness, NY; Howard Hughes Medical Institute, Medical Fellows Program. Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National institutes of Health under Award Number TL1R001858. The content is solely the responsibility of the authors and does not necessarily represent the official view of the National Institute of Health. We would also like to acknowledge Katherine A. Davoil for assisting with sectioning/staining the ocular histology and Dr. Julia K. Polat for scoring the corneal fluorescein images.
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41598-017-17869-y
DO - 10.1038/s41598-017-17869-y
M3 - Article
C2 - 29235530
AN - SCOPUS:85038412235
SN - 2045-2322
VL - 7
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 17527
ER -