Research Summary: Autophagy and cellular senescence in ocular hypertension and neurodegeneration in glaucoma.  

Research Description: Current efforts in my laboratory are focused on investigating a potential relationship between impairment of the autophagy lysosomal pathway and glaucoma in the aging eye. To address this fundamental question, my laboratory has developed three major independent, but yet interconnected, research programs:  

1. To investigate a role of autophagy in the physiology and pathophysiology of the trabecular meshwork (TM)/Schlemms’s canal (SC) outflow pathway: The TM/SC is a complex tissue located in the anterior segment of the eye responsible of maintaining proper levels of intraocular pressure (IOP). Failure of this tissue function is associated with increase risk in developing glaucoma, a potentially permanent blinding disease, affecting more than 70 million people worldwide. My lab is focused on studying the regulation of autophagy under mechanical stretch and shear stress conditions in TM cells.

2. To investigate a role of autophagy neurodegeneration in glaucoma: The exact molecular mechanisms triggering retinal ganglion cell death and axonal degeneration in glaucoma are still not fully understood. My lab is investigating the independent contribution of autophagy to apoptotic RGC death and axonal degeneration in acute injury and chronic hypertensive experimental models of glaucoma. Identification of the early critical molecular events in RGCs in response to elevated IOP would add to our understanding of the nature of glaucomatous injury and provide potential targets for neuroprotective strategies for the treatment of glaucoma.

3. Mechanisms of aging in the trabecular meshwork: Aging is the primary risk factor for ocular hypertension and glaucoma. Yet, the mechanisms by which aging predisposes to disease are not entirely understood. Our lab previously reported the accumulation of senescent cells in the TM from glaucoma donors. Our goal now is to investigate the potential cellular mechanisms by which senescent cells accumulate in the outflow pathway and contribute to ocular hypertension and glaucoma.