Advisory Committee Chair
Maria B Grant
Advisory Committee Members
marina Gorbatyuk
Janene Sims
Lawrence C Sincich
Mervin C Yoder
Document Type
Dissertation
Date of Award
2023
Degree Name by School
Doctor of Philosophy (PhD) School of Optometry
Abstract
The hematopoietic system, which resides in the bone marrow in adults, maintains the constant turnover of blood cells in the circulatory system and supplies inflammatory/vascular reparative cells to the retina. Chronic metabolic diseases disrupt hematopoietic homeostasis, suppressing the generation of bone marrow-derived reparative cells in favor of pro-inflammatory cells. While much research has been done on development and disease-associated changes in hematopoiesis in the long bones and how mobilization to the retina is affected, the calvarium's hematopoiesis is underexplored. This dissertation investigated hematopoiesis in postnatal development and in disease, comparing calvarium hematopoiesis to that of long bones. The findings showed that hematopoietic cells are recruited into the retina prenatally, distributed over the entire retina at birth and are critical for retinal angiogenesis in development. In addition, the calvarial marrow showed delayed hematopoietic development, delayed reconstitution of blood but enhanced engraftment of hematopoietic stem and progenitor cells (HSPCs) compared to long bones. Using retina ischemia-reperfusion injury model, it was observed that the calvaria marrow contributes more neutrophils and myeloid angiogenic cells (MACs) to the retina than the long bones following acute injury, even though the proportion of neutrophils and MACs at baseline were not significantly different between the two compartments. In chronic type 2 diabetes, it was observed that the calvarial marrow showed a resistance to the damaging effects of type 2 diabetes. The calvarium underwent slower bone deterioration, reduced buildup of fat content and less vascular degeneration compared to the tibia during chronic type 2 diabetes. This cumulatively resulted in a relative preservation of hematopoietic stem and progenitor cell function and an increase in erythroid lineage cells in the calvarial marrow and may explain, in part, why diabetic retinopathy is delayed in its development as the source of reparative cells for the retina comes from this protected compartment. Taken together, this dissertation has uncovered novel details about intramedullary hematopoiesis that shows that hematopoiesis in different bone marrow compartments is functionally different and important for the development of a healthy retina. It also highlights the significance of the calvaria bone marrow as a special source of reparative cells for the retina and survival of HSPCs and also a potential therapeutic target for delivery of therapeutic agents aimed at preventing or treating diabetic bone marrow damage and retinopathy.
Recommended Citation
Asare-Bediako, Bright, "Differential Recruitment of Bone Marrow-Derived Cells Into the Injured Retina" (2023). All ETDs from UAB. 48.
https://digitalcommons.library.uab.edu/etd-collection/48