Shedding Light on Sjögren’s and Dry Eye from the Hamm-Alvarez Lab
A Focus on Research – An Impact on Patient Care
“One day, it is our hope that our research will take us one step further in creating specialized therapeutics such as immunosuppressant drugs to treat SS as well as other autoimmune diseases,” – Hamm-Alvarez
Sarah Hamm-Alvarez, PhD, Professor of Ophthalmology and Pharmacology and Pharmaceutical Sciences, has devoted her career to understanding and developing treatments for Sjögren’s syndrome (SS), a debilitating eye condition that afflicts millions of Americans.
Interferon-gamma treatment in vitro elicits some of the changes in cathepsin s and antigen presentation characteristic of lacrimal glands and corneas from the NOD mouse model of Sjögren’s syndrome. – Hamm-Alvarez et al, PLoS one, 2017, p1-21.
Sjögren’s syndrome (SS) is an inflammatory autoimmune disease that affects over 4 million people nationwide. In addition to changes in your oral health, SS can cause severe dry eye. The disease, which affects 1 in 10 people with dry eye and often encompasses those with the most severe dry eye symptoms, impacts the lacrimal gland, which is responsible for tear production. Patients afflicted experience severe eye pain, burning and itchiness, causing damage to the corneal or outer-most surface of your eye. Those who suffer often go undiagnosed for years, delaying treatment for this debilitating disease.
Researchers in the Hamm-Alvarez group have made great strides in understanding the mechanisms by which the lacrimal gland promotes dryness and inflammation of the eye. In addition to a biomarker, the cathepsin S protein, found only in tears of patients with SS, additional tear biomarker proteins have been discovered by the Hamm-Alvarez group that are specific to the disease in the tear film of SS patients. Through extensive pre-clinical studies in the NOD mouse model of SS they have focused on studying the origins of the changes in protein secretory profiles in SS patients. These investigators have found a member of the interferon family of cytokines, interferon-γ (IFN-γ), is activated early in inflammation of the lacrimal gland. Moreover, when the secretory cells of the lacrimal gland are exposed to IFN-γ, some of the secretory changes including the increased secretion of cathepsin S are induced, suggesting that this is a major trigger of secretory dysfunction. The key findings in this study have lead these researchers to postulate that such cytokines act as triggers in initiating the disease.
Identification of a greater number of tear biomarkers specific for SS may lead to earlier diagnosis in patients as it allows for more sensitive diagnostic testing. Understanding how SS is triggered and the underlying mechanism will allow researchers to develop more specific therapies in treating non-autoimmune vs autoimmune dry eye.
The Hamm-Alvarez group is working towards developing novel immunosuppressant therapies and new more effective drug delivery mechanisms by which one can target SS. Most recently the Hamm-Alvarez group and collaborators presented a study characterizing the tear film proteins in those with SS-associated dry eye disease versus non-autoimmune mediated dry eye disease at this year’s American Academy of Ophthalmology in New Orleans. The study found elevated levels of several proteins in the tear film in SS patients relative to those with simple dry eye disease which may lead to enhanced diagnosis.