The Role of SFLT-1 in Corneal Avascularity

Hdl Handle:
http://hdl.handle.net/10675.2/343999
Title:
The Role of SFLT-1 in Corneal Avascularity
Authors:
Ambati, Balamurali K.
Abstract:
Ocular vascular compartmentalization is manifested by certain structures richly vascularized adjacent to normally avascular ones (e.g., the limbus next to the cornea or the retina next to the vitreous) and is necessary for optical transparency in the visual axis. Vision-threatening corneal angiogenesis can be caused by disease, aging, infection, or trauma. The basis of the cornea's avascularity has long been obscure. Although the absence of blood vessels in the cornea was known to the ancients such as Susruta (Sharma 2001) and Galen (Magnus 1999) millennia ago, only in the last century were angiostatic substances postulated to underpin corneal avascularity (Meyer & Chaffee 1940). Because of its avascularity and ease of accessibility the cornea has been a proving ground for testing antiangiogenic strategies for over 30 years (Gimbrone et al. 1974). Despite the cornea's widespread use as a readout template for anti-angiogenesis testing, the molecular foundations of corneal avascularity remain unclear. In the last decade, numerous anti-angiogenic molecules such as angiostatin, endostatin, interleukin-1 receptor antagonist, pigment epithelium derived factor, and thrombospondins were identified in the cornea (Chang et al. 2001). None of these molecules, however, is singly requisite for corneal avascularity because mice deficient in any of them retain normal corneal avascularity (Wiegand et al. 2004; Cursiefen et al. 2004; Bugge et al. 1995; Fukai et al. 2002; Hirsch et al. 1996), supporting the view of multiply redundant mechanisms of corneal avascularity. This study aims to elucidate the role of sFlt-1 in the preservation of corneal avascularity. This project applies RNA interference, a promising new efficient and specific molecular technology that targets specific mRNAs, to elucidate mechanisms of normal corneal avascularity. Other strategies employed include genomic and protein-based deletion of target molecules and cross-species protein expression profiles. We hypothesize that corneal avascularity is maintained at least in part by extracellular soluble VEGF receptor-1 (sVEGFR-1, also known as and henceforth referred to as sFlt-1).
Affiliation:
Vascular Biology Center
Issue Date:
Mar-2008
URI:
http://hdl.handle.net/10675.2/343999
Additional Links:
http://ezproxy.gru.edu/login?url=http://search.proquest.com/docview/304402369?accountid=12365
Type:
Dissertation
Appears in Collections:
Theses and Dissertations

Full metadata record

DC FieldValue Language
dc.contributor.authorAmbati, Balamurali K.en
dc.date.accessioned2015-01-30T20:11:21Z-
dc.date.available2015-01-30T20:11:21Z-
dc.date.issued2008-03-
dc.identifier.urihttp://hdl.handle.net/10675.2/343999-
dc.description.abstractOcular vascular compartmentalization is manifested by certain structures richly vascularized adjacent to normally avascular ones (e.g., the limbus next to the cornea or the retina next to the vitreous) and is necessary for optical transparency in the visual axis. Vision-threatening corneal angiogenesis can be caused by disease, aging, infection, or trauma. The basis of the cornea's avascularity has long been obscure. Although the absence of blood vessels in the cornea was known to the ancients such as Susruta (Sharma 2001) and Galen (Magnus 1999) millennia ago, only in the last century were angiostatic substances postulated to underpin corneal avascularity (Meyer & Chaffee 1940). Because of its avascularity and ease of accessibility the cornea has been a proving ground for testing antiangiogenic strategies for over 30 years (Gimbrone et al. 1974). Despite the cornea's widespread use as a readout template for anti-angiogenesis testing, the molecular foundations of corneal avascularity remain unclear. In the last decade, numerous anti-angiogenic molecules such as angiostatin, endostatin, interleukin-1 receptor antagonist, pigment epithelium derived factor, and thrombospondins were identified in the cornea (Chang et al. 2001). None of these molecules, however, is singly requisite for corneal avascularity because mice deficient in any of them retain normal corneal avascularity (Wiegand et al. 2004; Cursiefen et al. 2004; Bugge et al. 1995; Fukai et al. 2002; Hirsch et al. 1996), supporting the view of multiply redundant mechanisms of corneal avascularity. This study aims to elucidate the role of sFlt-1 in the preservation of corneal avascularity. This project applies RNA interference, a promising new efficient and specific molecular technology that targets specific mRNAs, to elucidate mechanisms of normal corneal avascularity. Other strategies employed include genomic and protein-based deletion of target molecules and cross-species protein expression profiles. We hypothesize that corneal avascularity is maintained at least in part by extracellular soluble VEGF receptor-1 (sVEGFR-1, also known as and henceforth referred to as sFlt-1).en
dc.relation.urlhttp://ezproxy.gru.edu/login?url=http://search.proquest.com/docview/304402369?accountid=12365en
dc.rightsCopyright protected. Unauthorized reproduction or use beyond the exceptions granted by the Fair Use clause of U.S. Copyright law may violate federal law.en
dc.subjectAngiogenesis Inhibitorsen
dc.subjectAngiostatinsen
dc.subjectGenomicsen
dc.subjectEndostatinsen
dc.titleThe Role of SFLT-1 in Corneal Avascularityen
dc.typeDissertationen
dc.contributor.departmentVascular Biology Centeren
dc.description.advisorCaldwell, Ruth B.en
dc.description.committeeAkhtar, Rashid; Atherton, Sally; Catravas, John; Nussbaum, Julianen
dc.description.degreeDoctor of Philosophy (Ph.D.)en
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