Dry eye disease is a multifactorial ocular disease associated with substantial medical expenses and significant impairments of quality of life and workplace productivity. Socioeconomic estimates attribute an annual burden of $50 billion to U.S. society. Current management of dry eye disease involves anti-inflammatory and immunomodulatory drugs, such as ophthalmic cyclosporine (Restasis®) or the integrin lymphocyte function-associated antigen-1 (LFA-1) antagonist, lifitegrast (Xiidra®). Surgical management offers the last resort when topical drugs fail to alleviate dry eye symptoms.
Clinically, dry eye disease is an umbrella term that describes ocular surface disease associated with various different etiologies, and encompasses aqueous deficient and evaporative dry eye, ocular graft-vs-host disease (a complication of bone marrow transplant), autoimmune dry eye (e.g. associated with Sjögren’s syndrome), and chronic ocular symptoms associated allergies.
One major challenge in drug discovery for dry eye disease has been a lack of standardized experimental methods and paradigms that can help elucidate the pathophysiology of the various facets of the disease but also to test drug candidates such that these preclinical data can be predictive for success in phase trials
The major focus of our research program has been to rigorously refine existing models for dry eye disease, standardize and validate them against the clinical standard of care for dry eye disease, Restasis®, and to use pharmacological agents and drug candidates to both, gain mechanistic insight into the disease pathology and accelerate drug discovery for dry eye disease.
We currently have several projects on dry eye disease in the lab and are actively recruiting graduate students and postdocs to join our group:
Glaucoma is the leading cause of irreversible blindness worldwide and causes a substantial burden on the affected individual, caregivers, and society alike. It is estimated that approx. 6 mi Americans are affected by glaucoma.
Primary open-angle glaucoma (POAG) is the most common form of glaucoma and defined as any glaucoma in which the angle of the anterior chamber remains open, but the exit of aqueous through the trabecular meshwork is diminished. This leads to an abnormal balance of secretion and drainage of aqueous through the trabecular meshwork and uveoscleral outflow pathways, ultimately resulting in elevated intraocular pressure (IOP). While currently available therapies can lower IOP to prevent further ON damage, visual field loss and death of both RGCs and ONHAs continues, highlighting the need for novel treatment strategies.
Optic nerve head astrocytes are the major cell type in the non-myelinated region of the optic nerve head and provide structural, metabolic and trophic support to the optic nerve. Under pathological conditions, such as primary open angle glaucoma, these cells undergo a process called reactive astrocytosis (or astrogliosis). The ensuing changes in the structural and biomechanical properties of the optic nerve head manifest as optic nerve “cupping” and are used clinically as a diagnostic criterion for the progression of glaucoma.
In our Laboratory, we are particularly interested in deciphering the mechanisms contributing to the reactive astrocytosis and to discovering novel drug targets that can stop the progressive cascade of glaucomatous changes.
We currently have several ongoing projects on glacucoma in the lab:
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