Br J Ophthalmol 1999;83:486-494 ( April )
Immunolocalisation of the VEGF receptors FLT-1, KDR, and FLT-4 in
diabetic retinopathy
Gillian Smith,
David McLeod,
David Foreman,
Mike Boulton
University
Department of Ophthalmology, Manchester Royal Eye Hospital, Manchester
Correspondence to: Professor Mike Boulton, Department of Optometry and Vision Sciences,
Cardiff University, Redwood Building, PO Box 905, Cardiff CF1 3XF.
Accepted for publication 25 November 1998
AIM To determine the
spatial and temporal changes in the staining pattern of the VEGF
receptors FLT-1, KDR, and the putative receptor FLT-4 during the
pathogenesis of diabetic retinopathy.
METHODSImmunohistochemical
localisation of VEGF receptors, using antibodies against FLT-1, FLT-4,
and KDR, was carried out on specimens of normal human retina (n=10),
diabetic retinas (a) with no overt retinopathy (n=12), (b) with
intraretinal vascular abnormalities but no proliferative retinopathy
(n=5), (c) with active proliferative retinopathy (n=6), and (d) with no
residual proliferative retinopathy after scatter photocoagulation
therapy (n=14), and surgically excised diabetic fibrovascular membranes
(n=11). The degree and pattern of immunostaining was recorded.
RESULTSFLT-1 staining
was apparent in the retinas from both non-diabetic and diabetic
retinas; weak to moderate staining was generally confined to the inner
nuclear layer, the ganglion cell layer, and the retinal vessels during
all stages of the disease process. Staining of the retinal vessels was
raised in diabetic tissue compared with non-diabetic tissue. The
preretinal vessels of the diabetic subjects stained moderately to
intensely for FLT-1. In contrast with FLT-1 staining minimal
immunostaining for KDR was demonstrated in the non-diabetic eyes and
the unlasered eyes; however, weak staining for KDR was observed in the
inner nuclear layer and the ganglion cell layer of the unlasered eyes
with diabetic changes. In those retinas with preretinal
neovascularisation KDR immunoreactivity was moderate to intense in the
intra- and preretinal vessels. However, in the excised membranes, where
the vessels may have been in a quiescent state, the levels of KDR were
weak to moderate. After apparently successful laser treatment KDR
staining was reduced in the intraretinal vessels. Minimal FLT-4
staining was observed throughout normal eyes while weak to moderate
FLT-4 staining was generally confined to the inner nuclear layer and the ganglion cell layer of the unlasered diabetic eyes. Weak to moderate levels of FLT-4 staining were observed in the intraretinal vessels except after apparently successful laser treatment where reduced levels of staining were observed. Weak to moderate staining was
observed in the preretinal vessels.
CONCLUSIONSThis study
supports a role for FLT-1, KDR, and possibly FLT-4 in the pathogenesis
of diabetic retinopathy; however, their specific roles in the
progression of the disease may differ.
Keywords:
vascular endothelial growth
factor;
VEGF receptors;
diabetic retinopathy
© 1999 by British Journal of Ophthalmology
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