Protecting vessel loss in the eyes of premature infants
As premature infants often have under-developed lungs, oxygen is administered following birth. One devastating side effect, however, is the development of retinopathy of prematurity (ROP), whereupon oxygen administration to the infant suppresses the expression of essential growth factors that promote the development of retinal blood vessels, resulting in blindness. In the July 1 issue of the Journal of Clinical Investigation, a study by researchers at Harvard Medical School and Childrens Hospital, Boston investigating the development of the retinal vasculature in mice demonstrates that specific activation of the receptor VEGFR-1 by the growth factor PlGF-1 protects against oxygen-induced vessel loss.
ROP occurs in two distinct stages. First, exposure to high levels of oxygen causes obliteration of immature retinal vessels. The second phase, initiated upon return to breathing normal air, results in an adverse overcompensation of new vessel growth. The new vessels are excessive in number and often leaky. The inner membrane of the retina can be breached, whereby vessels grow into the vitreous of the eye causing retinal detachment and blindness.
The process of vasculature development is mediated in part by the growth factor VEGF. It had been shown previously that vessels can be rescued by administration of VEGF, suggesting that VEGF might be used in the treatment of ROP. However, this theory presents a double-edged sword as VEGF also stimulates abnormal vessel growth that can ultimately result in leaky vessels.
In order to wisely skirt this catastrophic event, Lois E. H. Smith and colleagues utilized placental growth factor-1 (PlGF-1), which exclusively activates the VEGF receptor-1 (VEGFR-1). The authors demonstrate that the administration of PlGF-1 protects against oxygen-induced vessel loss without provoking neovascularization. Unlike VEGF, which interacts with both forms of the VEGF receptor (VEGFR-1 and VEGFR-2), PlGF-1 only binds VEGFR-1.
These results suggest that PlGF-1 could be harnessed as a therapeutic agent to stabilize vessel growth. “Clearly, the case of ROP is unique, considering the defined nature of the pathogenic insult, its relatively short duration, and its predetermined onset. These characteristics, in conjunction with the fact that the vitreous is a close, immunoprivileged compartment and that the superficial retinal vessels are accessible to injected reagents, increase the likelihood of success” states Dr. Eli Keshet, from the Hebrew University-Hadassah Medical School in Jerusalem, Israel in his accompanying commentary. In addition, as it is the specific activation of VEGFR-1, and not VEGFR-2, that protects against oxygen-induced vessel loss, targeting VEGFR-1 with additional pharmacological activators may also control vessel degeneration in ROP and other retinopathies.
TITLE: Selective stimulation of VEGFR-1 prevents oxygen-induced retinal vascular degeneration in retinopathy of prematurity
Lois E. H. Smith
The Childrens Hospital, Boston, Massachusetts, USA.
View the PDF of this article at: https://www.the-jci.org/press/17808.pdf
Preventing pathological regression of blood vessels
The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
View the PDF of this commentary at: https://www.the-jci.org/press/19093.pdf
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