Angiogenesis is required for proper development of the embryonic circulatory system and is an important step in the progression of many eye diseases, including retinopathy of prematurity (ROP). Therefore, understanding how the normal regulatory systems in the endothelium keep angiogenesis in check has great clinical implications. Platelet endothelial cell adhesion molecule-1 (PECAM-1) is an important regulator of angiogenesis. We have shown that multiple isoforms of PECAM-1 are expressed in vascular beds of different tissues in a developmentally regulated fashion. The ability of these isoforms to differentially activate intracellular signaling pathways suggests specific roles for these isoforms during vascular development and angiogenesis. However, the physiological role PECAM-1 and its isoforms play in these processes requires further investigation. The main objective of this proposal is to delineate the physiological role of PECAM-1 and its isoforms in retinal vascular development and angiogenesis, as well as in regulation of retinal EC adhesive and migratory properties, and to elucidate the function of genes whose endothelium expression is differentially regulated by PECAM-1. Specifically, we will demonstrate the role of PECAM-1 in the development of retinal vasculature and neovascularization and determine how these processes are affected in the absence of PECAM-1. We will determine the expression pattern of PECAM-1 isoforms during retinal vascular development and neovascularization, as well as in retinal endothelial cells (EC). We will evaluate the specific roles of PECAM-1 isoforms in the regulation of EC adhesion and migration. To further elucidate PECAM-1's mechanism of action, we will identify and perform functional studies of genes such as endoglin and connective tissue growth factor whose endothelium-specific expression is differentially affected by the lack of PECAM-1. These studies will provide insight into the physiological role of PECAM-1 in retinal vascular development and angiogenesis and in modulation of EC adhesion and migration. This knowledge will be instrumental in the development of new treatment modalities for a variety of eye diseases with a neovascular component.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
Project #
Application #
Study Section
Biology and Diseases of the Posterior Eye Study Section (BDPE)
Program Officer
Shen, Grace L
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Wisconsin Madison
Schools of Medicine
United States
Zip Code
Ghanian, Zahra; Staniszewski, Kevin; Jamali, Nasim et al. (2016) Quantitative Assessment of Retinopathy Using Multi-parameter Image Analysis. J Med Signals Sens 6:71-80
Park, Sunyoung; Sorenson, Christine M; Sheibani, Nader (2015) PECAM-1 isoforms, eNOS and endoglin axis in regulation of angiogenesis. Clin Sci (Lond) 129:217-34
Larsen, Michele Campaigne; Bushkofsky, Justin R; Gorman, Tyler et al. (2015) Cytochrome P450 1B1: An unexpected modulator of liver fatty acid homeostasis. Arch Biochem Biophys 571:21-39
Ghanian, Zahra; Maleki, Sepideh; Park, SunYoung et al. (2014) Organ specific optical imaging of mitochondrial redox state in a rodent model of hereditary hemorrhagic telangiectasia-1. J Biophotonics 7:799-809
Sorenson, Christine M; Wang, Shoujian; Gendron, Robert et al. (2013) Thrombospondin-1 Deficiency Exacerbates the Pathogenesis of Diabetic Retinopathy. J Diabetes Metab Suppl 12:
Park, Sunyoung; Dimaio, Terri A; Liu, Wei et al. (2013) Endoglin regulates the activation and quiescence of endothelium by participating in canonical and non-canonical TGF-? signaling pathways. J Cell Sci 126:1392-405
Palenski, Tammy L; Sorenson, Christine M; Jefcoate, Colin R et al. (2013) Lack of Cyp1b1 promotes the proliferative and migratory phenotype of perivascular supporting cells. Lab Invest 93:646-62
Shah, Gul N; Price, Tulin O; Banks, William A et al. (2013) Pharmacological inhibition of mitochondrial carbonic anhydrases protects mouse cerebral pericytes from high glucose-induced oxidative stress and apoptosis. J Pharmacol Exp Ther 344:637-45
Aghdam, Saeed Yadranji; Gurel, Zafer; Ghaffarieh, Alireza et al. (2013) High glucose and diabetes modulate cellular proteasome function: Implications in the pathogenesis of diabetes complications. Biochem Biophys Res Commun 432:339-44
Palenski, Tammy L; Sorenson, Christine M; Sheibani, Nader (2013) Inflammatory cytokine-specific alterations in retinal endothelial cell function. Microvasc Res 89:57-69

Showing the most recent 10 out of 33 publications