Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022575 (keratoconjunctivitis sicca)
 772 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dry eye disease (DED), also known as keratoconjunctivitis sicca, is an ocular surface disease characterized by T-cell-mediated inflammation. Current therapeutics, such as immunosuppressive agents, act to suppress the clinical signs and inflammation. However, long-term usage of these treatments can cause severe side effects. In this study, we present an alternative therapeutic approach that utilizes a histone deacetylase inhibitor (HDACi) to regulate transcription of a variety of immunomodulatory genes. Specifically, HDACi have emerged as a potential anti-inflammatory agent, which can modulate the functions of a subset of suppressive T lymphocytes known as regulatory T cells (Tregs), enhancing FoxP3 acetylation and subsequently guarding the transcription factor from proteasomal degradation. Here, a specific HDACi known as SAHA (suberoylanilide hydroxamic acid) was formulated to controllably release in the lacrimal gland. Intralacrimal gland injection of PLGA-based SAHA microspheres prevented clinical signs of DED in mice with Concanavalin A-induced DED, reduced expression of pro-inflammatory cytokines, and increased expression of FoxP3 in the lacrimal glands. Murine T cell culture experiments also revealed that SAHA decreased effector T cell proliferation and enhanced suppressive function of Tregs in co-cultures of Tregs and effector T cells.
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PMID:Controlled release of an HDAC inhibitor for reduction of inflammation in dry eye disease. 2952 28