Vision Science Research Seminar Series lecture: Theme- New directions for diagnosis and treatment of autoimmune-mediated dry eye in Sjögren’s disease

Biography

Dr. Hamm-Alvarez is Professor of Ophthalmology and of Pharmacology and Pharmaceutical Sciences at USC, where she also serves as the Associate Dean for Basic and Translational Research at the Keck School of Medicine.  She completed her PhD in Biochemistry and postdoctoral training in Cell Biology, both at Duke University in Durham, North Carolina, before joining the University of Southern California as a faculty member.  Her research investigates the physiology and pathophysiology of the ocular surface system, a connected group of tissues and biofluids that together maintain visual acuity and protect the integrity of the cornea.  Her particular area of focus is understanding the mechanisms responsible for production and secretion of tear proteins from the lacrimal gland, investigating changes in these processes associated with the development of dry eye disorders, and identifying new molecular targets and treatment modalities for treatment of dry eye.  The laboratory’s primary focus is in improving the diagnosis and treatment of the autoimmune-mediated dry eye associated with Sjögren's disease.  Her research spans work in simple cell model systems, to murine models of disease and to biomarker discovery in clinical specimens.

Abstract

Sjögren's disease (SjD) is a prevalent autoimmune disease characterized by lymphocytic infiltration and loss of function of the moisture-producing lacrimal and salivary glands, resulting in autoimmune-mediated dry eye and dry mouth.  SjD-associated dry eye is typically severe, and can lead to compromised visual acuity, corneal scarring, and vision loss.  SjD patients also develop a host of systemic and debilitating rheumatic symptoms.  Although SjD affects approximately 1% of the population, the disease is challenging to diagnose while dedicated treatment options are lacking, particularly for its ocular manifestations.  In murine models of SjD-associated dry eye, our group has utilized a variety of “omics” techniques to characterize early changes in tear film composition that represent potential diagnostic biomarkers of SjD-associated dry eye and also provide insights into the mechanisms underlying the development of autoimmune dacryoadenitis (inflammation of the lacrimal gland) that is a hallmark feature of the disease.  These studies are complemented by our characterization of early pathological changes occurring in the acinar cells of the lacrimal gland (which produce and secrete tear proteins) that accompany the onset of autoimmune dacryoadenitis in these murine models.  Our findings collectively implicate increased signaling through NLRP3 inflammasomes and RAGE (receptor for advanced glycation end products) as well as defective acinar autophagy as early events underlying the onset and development of autoimmune dacryoadenitis, suggesting these pathways as potential new targets for therapeutic development for SjD-associated dry eye.