Paloma B. Liton, PhD, Principal Investigator
Duke Eye Center
AERI 4004 Erwin Road
Durham, NC 27710
Phone: 919 681 4085
Fax: 919 684 8983
- Licenciature in Molecular Biology, Universidad Autonoma De Madrid, Spain, 1995
- PhD in Molecular Biology, Universidad Autonoma De Madrid, Spain, 2001
Postdoctoral Fellowship, Duke University, Department of Ophthalmology
Research Summary: Autophagy lysosomal pathway in ocular physiology and pathophysiology.
Research Description: The long-term goal of our research program is elucidating the molecular mechanisms underlying the normal physiology and the pathophysiology of the outflow pathway. The outflow pathway is a complex tissue located in the anterior segment of the eye responsible of maintaining proper levels of intraocular pressure. Failure of this tissue with aging is associated with increase risk in developing Primary Open Angle Glaucoma, a blinding disease, affecting more than 70 million people worldwide. At present it is not known why this tissue fails with aging and in disease. To address this fundamental question, my laboratory has developed two major independent, but yet interconnected, research programs:
- To investigate a role of autophagy in outflow physiology/pathophysiology and neurodegeneration in glaucoma: The lysosomal pathway is the major proteolytic system responsible for the continuous turnover of cellular organelles and most intracellular and extracellular long-lived proteins. Substrates are delivered to the lysosomal system by three different routes:
- (i) the biosynthetic route, which delivers the digestive enzymes synthesized in the rough ER
- (ii) the endocytic pathway, by which extracellular molecules are internalized by receptor-mediated endocytosis or phagocytosis and delivered to the early endosomes or to the phagosomes, respectively; and
- (iii) the autophagic pathway, responsible for the destruction of most long-lived endogenous proteins and damaged or obsolete organelles which are engulfed in autophagic vesicles. Failure of the lysosomal system is suspected to contribute to the progressive cellular dysfunction commonly associated with aging and age-related diseases. By using in vitro and in vivo models, we are investigating the autophagic response of trabecular and retinal ganglion cells to different types of stress.
- To explore a novel role of phagocytosis in aqueous humor outflow regulation: Trabecular meshwork cells are known to be able to avidly phagocyte particulate material and debris. Phagocytosis is thought to have an important role in the normal functioning of the outflow pathway by keeping the drainage channels free of obstructive material or debris, which otherwise might block the flow of aqueous humor. Indeed, abnormalities in phagocytosis have been postulated to contribute to the development of certain types of glaucoma, in particular in exfoliative, pigmentary, phagolytic, and other obstructive glaucomas. At the cellular level, several studies have shown the detachment of TM cells from the trabecular beams following phagocytosis in vivo and in vitro, as well as short-term loss in cell-matrix cohesiveness in cell culture conditions. Our laboratory is investigating the molecular pathways and molecular mechanisms activated in trabecular meshwork cells upon phagocytic challenge.