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Vessel stability in the Edinburgh model of retinopathy of prematurity : investigation of mural cell coverage & growth factor expression

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YaqoobZ_2003redux.pdf (35.48Mb)
Date
2003
Author
Yaqoob, Zeenat
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Abstract
 
 
Retinal blood vessels consist of endothelial tubules surrounded by a single layer of smooth muscle cells or pericytes, collectively called the mural cells. Coverage of the vessel with mural cells is suggested to signal their stability, and requires the actions of several locally secreted growth factors including: platelet-derived growth factor, which promotes mural cell migration and proliferation; transforming growth factor-/)1, that induces the differentiation of precursors cells into pericytes and smooth muscle cells; and the angiopoietins, for maintaining the interactions between endothelial cells and pericytes.
 
Stability of blood vessels is believed to be compromised in retinopathy of prematurity (ROP), a potentially binding eye disease characterised by the invasion of the vitreous by proliferating retinal blood vessels. In the past the use of high oxygen levels for the treatment of extremely premature infants was associated with the incidence of this condition. However, it was recently suggested that rather than absolute oxygen levels, the variability of the transcutaneous (blood) oxygen levels within clinically 'safe' limits during the first two weeks of life may be more important in ROP. Thus, a clinically relevant animal model of ROP was developed (Edinburgh model). The first 14 days of the transcutaneous oxygen profile of an infant who developed severe ROP was selected and converted into percentage inspired oxygen levels to produce the equivalent arterial oxygen in a rat. The aims of this thesis were to investigate mural cell coverage and the expression of the factors suggested to participate in vessel stabilisation during normal retinal development and in the Edinburgh model.
 
Rat pups were raised in room air or exposed to the oxygen regime of the Edinburgh model from birth to postnatal days 2, 7 and 14. The pups were then killed, the eyes enucleated and analysed for mural cell coverage and expression of platelet-derived growth factor-ß₁, transforming growth factor-/!i and angiopoietin-2 using immunohistochemical, Western blotting, electron microscopy and in situ hybridisation techniques
 
In comparison to room air raised pups, the retinal vasculature of the pups raised in the variable oxygen regime had reduced mural cell coverage; smooth muscle cell coverage was only slightly reduced, however there was a marked and significant reduction in pericyte coverage. The protein expression of both platelet-derived growth factor-ß₁ and transforming growth factor-ß were also reduced. Unfortunately, the analysis of angiopoietin-2 mRNA expression was inconclusive due to insensitive detection methods.
 
In conclusion, the reduction in mural cell coverage and in the expression of platelet derived growth factor and transforming growth factor-ß₁ suggest that blood vessel stability is compromised in the Edinburgh model of retinopathy of prematurity.
 
URI
http://hdl.handle.net/1842/27722
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