Delineating the Role Of ECM Alterations in a Patient-Derived Hipsc-RPE-EC Co-Culture Model of Macular Degeneration
In macular degeneration, the light-sensing tissue in the back of our eye, called the retina, becomes damaged. In the retina, the retinal pigment epithelium (RPE) cells and their underlying vascular support system, the choroid, are the main cell types affected in age-related macular degeneration (AMD), the most common form, and in similar vision diseases. However, it is not known whether RPE or choroid cells are responsible for the disease. Therefore, our goal in this study is to identify whether loss of RPE or choroid cell function alone can cause the disease. This knowledge will help us to develop drug treatments that can make the affected cell types healthy again.
The overall goal of this project is to understand the role of different cells in the eye that are affected in macular degeneration, and which of them initiate disease processes culminating in visual dysfunction. We will use human induced pluripotent stem cells (hiPSCs) derived from patients with macular degeneration and unaffected control subjects to generate both RPE and endothelial cells (EC). We will then evaluate whether RPE and/or EC cells derived from patients with macular degeneration display different physical and functional characteristics than RPE and/or EC derived from unaffected individuals. Furthermore, because both RPE and EC can be affected in late-stage macular degeneration, we will determine whether defects in one cell type (RPE or EC cells) is sufficient to affect the properties of the other cell type (RPE/EC) when both cell types are cultured together.
The most innovative aspect of this study is that we are using patient-derived cells to study the disease mechanism of macular degeneration in the cell type(s) that are affected in the patient eyes (RPE and EC). Establishing a human model of macular degeneration composed of both affected cell type(s) (RPE and EC) to identify the specific role of each individual cell type has never been done before. Understanding the specific contribution of the RPE versus EC in disease development will have significant implications in the coming years for designing rational drug therapies targeting macular degeneration. Furthermore, a patient-derived human model of macular degeneration will allow us to test potential drug therapies in future studies.
About the Researcher
Ruchira Singh, PhD, is an assistant professor in the Departments of Ophthalmology and Biomedical Genetics at University of Rochester. She obtained her PhD in physiology from Kansas State University and completed her postdoctoral training in pharmacology at Yale School of Medicine and in stem cell research at University of Wisconsin-Madison. Her research program at University of Rochester derives from these strengths, with an integrated focus on retinal physiology, neurodegenerative diseases, stem cells, and pharmacology. The current projects in the laboratory are focused on using hiPSCs for 1) studying the pathophysiology of inherited and age-related macular degeneration and 2) creating complex retinal cell models to study intercellular interaction in retinal physiology and disease development. Dr. Singh also is interested in delineating the role of gene-environment interaction in retinal and neurodegenerative diseases. In addition to her BrightFocus grant, funding from the University of Rochester Research Award, Knight Templar Eye Foundation, Retina Research Foundation, and a Research to Prevent Blindness (RPB) Career Development Award supports her work.
"Unlike most biomedical researchers, my first experience of science was not in high school or even during my undergraduate education. It was an hourly job as a master’s of computer science graduate student at Kansas State University that introduced me to biomedical research. I joined my graduate studies lab as a web page designer and left four and a half years later with a doctoral degree in physiology. It was my passion for and fascination with research, along with the faith of fellow scientists and advisors, that enabled me to learn and bridge the gap in years of knowledge and learning.
Actually, my fascination with biomedical research occurred long before my PhD training. However, circumstances and life situations did not allow me to pursue this interest before. Born and brought up in a middle-class Indian family, I was taught early on that the sole purpose of education was to find a decent paying job to support one’s self and family. So like, many other Indians, I decided to pursue a career in computer science at the age of 14. However, fate had something else in store. At the age of 15, I met with a serious accident and was hospitalized for over four months. It was during this time that I became aware of the limitation of current medical knowledge in treatment of various diseases affecting the people surrounding me. If I would have been in a country like the United States, I would have immediately switched my career path to study biomedical sciences. However, being in a regimented education system like India‘s, I continued studying computer science, receiving a degree in computer science engineering. I moved to the United States to pursue a master’s degree in computer science engineering and hopefully computational research. But as fate would have it, I was destined to work in the field of my passion, biomedical research.
When I switched from computer science to biomedical research, 10 years ago, I was not sure if I would be able to make a difference, but nonetheless, I was certain that this is what I wanted to do for the rest of my life. Today, I know that I am on the right path and my work with patient-derived stem cells will one day lead to treatments and possibly cures for retinal and neurodegenerative diseases.
I would like to emphasize the importance of the BrightFocus Foundation grant to my research. I am an assistant professor (tenure track), I am in the early stages of my career and have only recently established my own independent lab. Thus, this grant is instrumental to my laboratory, allowing for the purchase of reagents and offering salary support for research personnel. I know that BrightFocus Foundation depends on the generous support of donations for macular degeneration research. Given this, I would sincerely like to thank the donors for funding my research project and moving my research program forward."
First published on: July 15, 2015
Last modified on: June 15, 2017