Although dry eye associated with Sjögren’s syndrome, an autoimmune disease that inflicts lacrimal gland and salivary glands, is the most severe form of dry eye, its etiology and management is poorly understood, with artificial tears being the primary choice for clinicians to alleviate dry eye symptoms only, without treating the root cause of the disease, i.e., autoimmune-mediated lacrimal gland deficiency. In the proposed studies, we will evaluate the effects of various formulations of rapamycin-a potent immunomodulatory agent that has been widely used in other autoimmune diseases, including those aided by elastin-like polypeptides (ELP), on ocular surface integrity, autoimmune dacryoadenitis, and select target gene expressions, by using a well-established Sjögren’s syndrome model, non-obese diabetic (NOD) mice. Results from these studies will enable us to gain valuable insights into the formulation and underlying mechanisms of rapamycin-based eye drops’ potential therapeutic effects for autoimmune-mediated dry eye, and help us collecting urgently needed preliminary data for a NIH large-scale grant resubmission focused on development of novel therapeutic approaches for autoimmune-mediated dry eye.

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