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

• Published in: Scientific reports 2017-12, Vol.7 (1), p.17527-9, Article 17527
• Main Authors: Ratay, Michelle L., Balmert, Stephen C., Acharya, Abhinav P., Greene, Ashlee C., Meyyappan, Thiagarajan, Little, Steven R.
• Format: Article
• Language: English
• Subjects: 13; 14/1; 631/154/152; 639/166/985; 64/60; Adoptive transfer; Animals; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Conjunctiva; Controlled release; Cornea; Delayed-Action Preparations; Disease Models, Animal; Dry Eye Syndromes - immunology; Dry Eye Syndromes - pathology; Dry Eye Syndromes - prevention & control; Eye; Eye diseases; Female; Goblet cells; Humanities and Social Sciences; Immunoregulation; Inflammation; Inflammation - immunology; Inflammation - pathology; Inflammation - prevention & control; Innervation; Interleukin 2; Interleukin-2 - administration & dosage; Lacrimal Apparatus - drug effects; Lacrimal Apparatus - immunology; Lacrimal Apparatus - pathology; Lacrimal gland and Nasolacrimal duct; Lymphocytes; Lymphocytes T; Mice, Inbred BALB C; Microspheres; multidisciplinary; Polymers; Rapamycin; Science; Science (multidisciplinary); Sirolimus - administration & dosage; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - metabolism; T-Lymphocytes, Regulatory - pathology; Transforming Growth Factor beta1 - administration & dosage; Transforming growth factor-b1
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-17869-y

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; T GF-β1, R apamycin (Rapa), and I L-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.