Maria Grant, MD, FARVO
Professor
Eivor and Alston Callahan Endowed Chair
Department of Ophthalmology and Visual Sciences
University of Alabama
Birmingham, Alabama, USA
email: mariagrant@uabmc.edu
Biography
Dr. Grant is the Eivor and Alston Callahan, M.D., Endowed Chair in Ophthalmology at the University of Alabama, Birmingham and a Fellow of ARVO. Her laboratory focuses on functional processes of stem cells (hematopoietic, embryonic, and induced pluripotent) and their potential to prevent or repair vascular degeneration in retinopathies associated with diabetes and hypoxia. More recently, her work has focused on understanding the gut-eye axis, particularly the link between gut barrier function and disruption of the blood retinal barrier in diabetes. Dr Grant’s research is currently funded by NEI/NIH while her work has also been supported by the Juvenile Diabetes Research Foundation and the American Heart Association. Her prolific publication record includes over 260 peer-reviewed research articles and 12 reviews and book chapters that have been cited over 21,000 times. Dr Grant has also been involved with 10 clinical trials related to the treatment of diabetic complications and currently has 13 issued and pending US and international patents. She currently serves on the Editorial Board of IOVS and American Heart Journal Plus: Cardiology Research and Practice. Dr Grant earned her undergraduate and medical degrees from the University of Florida, Gainesville, and completed her research fellowships from the University of Florida and the Johns Hopkins University.
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Abstract
Title: Hematopoietic stem/progenitor cells mobilize from distinct bone marrow compartments in response to retinal injury
Hematopoietic cells and vascular wall derived endothelial progenitors exist to restore function to damaged endothelium. Much like other tissues, the bone marrow suffers diabetic end-organ damage, including aberrant adipogenesis, mobilopathy and microangiopathy. Similarly, in diabetics with micro and macrovascular complications, the vascular endothelium is depleted of endothelial progenitor cells (endothelial colony forming cells; ECFC) adversely impacting vessel repair. iPSCs have been generated from many different cells type from both normal and diabetic individuals. iPSCs can be differentiated into hematopoietic cells and ECFCs for vascular repair. We demonstrate the use of a unique hiPSC-derived mesodermal population that promotes robust microvascular repair without any evidence of toxicity. This population was characterized based on expression of VEGFR2, NCAM, and APLNR (KNA+ cells). Both nondiabetic and diabetic donors were used to generate hiPSC lines, and in vitro and in vivo studies were performed to interrogate their function.
The next part of the presentation will discuss specialized bone marrow microenvironments, called niches, inside long and flat bones. The impact of diabetes on the bone marrow niches at different sites has not been studied. We show that the impact of diabetes is different in the calvaria marrow compartment compared to long bones. The calvarium undergoes slower bone deterioration, reduced buildup of fat content and less vascular degeneration compared to the tibia during chronic type 2 diabetes. Cumulatively, this results in a relative preservation of hematopoietic stem and progenitor cell function and an increase in erythroid lineage cells in the calvaria marrow during this period of chronic metabolic insult. Our study suggest that the calvarium is protected from the adverse consequences of diabetes longer than the other bone marrow compartments.