Publication: Upregulation of vascular endothelial growth factor (VEGF) in the retinas of transgenic
mice overexpressing interleukin-1ß (IL-1ß) in the
lens and mice undergoing retinal degeneration
Authors
Vinores, S.A. ; Xiao, W.H. ; Zimmerman, R. ; Whitcup, S.M. ; Wawrousek, E.F.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
IL-1ß is a pro-inflammatory agent associated
with angiogenesis and increased vascular permeability.
To determine whether IL-1ß elicits these responses
through an upregulation of VEGF, transgenic mice that
overexpress IL-1ß in the lens were evaluated at various
time points for the localization of VEGF, the location
and extent of blood-retinal barrier (BRB) breakdown,
and the origin and extent of neovascularization (NV). In
homozygous and heterozygous transgenic mice, but not
controls, intense VEGF immunoreactivity was scattered
throughout the retina at postnatal days 5-7 (P5-7), just
after the onset of inflammatory cell infiltration. VEGF
staining in the retina remained widespread, but weak
from P9-15. Beginning at P15, the intensity of VEGF
immunoreactivity achieved a second peak, which it
maintained through adulthood. This peak coincided with
significant retinal destruction due to massive
inflammation. The onset of BRB breakdown coincided
with the upregulation of VEGF (P5-7) and widespread
BRB breakdown was demonstrated from about P9. From
P9-12, aggregates of cells positive for Griffonia
simplicifolia isolectin-B4, a marker for vascular
endothelial cells, formed on the retinal surface. These
cells migrated into the retina at P12-15 with the more
superficial cells forming a network of vessels and the
deeper cells remaining in small clusters, thus
demonstrating that NV occurs much later than BRB breakdown. Non-transgenic FVB/N mice, which
undergo retinal degeneration beginning at about P9, also
demonstrate the latter peak of VEGF upregulation and
the accompanying BRB breakdown, but not the early
upregulation. VEGF immunostaining of transgenic and
non-transgenic mouse retinas was eliminated by preincubation
of the VEGF antibodies with VEGF peptide.
The data suggest that the early peak of VEGF upregulation (P5-7) and its accompanying BRB
breakdown is due to IL-1ß expression and is likely to be
dependent on inflammatory cell infiltration. The latter
peak appears to be related to retinal destruction.
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