Inhibition of Vascular
Endothelial Growth Factor-Induced Retinal Neovascularization by
Retinoic Acid in Experimental Retinopathy of Prematurity
H. OZKAN1, N. DUMAN1, A. KUMRAL1, B. KASAP1, E.
A. OZER1, B. LEBE2,
A. YAMAN3, T. BERK3, O. YILMAZ4, E. OZER2
1Department of Pediatrics, School of Medicine, 2Department of
Pathology, 3Department of Ophtalmology, 4Experimental Animal
Laboratory, School of Medicine, Dokuz Eylul University, Izmir,
Turkey
Received January 25, 2005
Accepted May 24, 2005
On-line available August 5, 2005
Summary
Vascular endothelial growth factor (VEGF) has an important role
in the pathogenesis of retinopathy of prematurity (ROP) and
inhibition of VEGF expression in the neovascular phase might
prevent destructive neovascularization in ROP. It is suggested
that retinoids exert a highly potent antiangiogenic activity by
inhibiting VEGF expression. The aim of this study was to
demonstrate the preventive effect of retinoic acid (RA) on the
VEGF-induced retinal neovascularization in a rat model of ROP.
Wistar albino rats were placed into incubators at birth and
exposed to an atmosphere alternating between 50 % and 10 % O2
every 24 hours. After 14 days, the animals were removed to room
air and received either an intraperitoneal injection of RA (5
mg/kg/day) (n=9) or saline (n=4) daily for six days, and
sacrificed at 21 days. Other rats (n=4) were raised in room air
and served as age-matched controls. The globe of each eye was
cut through the cornea and embedded in paraffin. Serial sections
were stained with hematoxylin-eosin for quantification of
neovascular nuclei. The avidin-biotin peroxidase method was
performed for evaluation of VEGF expression. The average number
of neovascular nuclei was significantly lower in the control
group compared to that in the ROP groups. In addition, it
significantly decreased in the RA-treated ROP group compared to
that of the saline-administrated ROP group. VEGF immunostaining
was overall negative in room air-exposed rats. The VEGF
immunostaining score significantly decreased in the RA-treated
ROP group compared to that in the saline-administered ROP group.
RA treatment might be beneficial in preventing
neovascularization resulting from oxygen-induced retinopathy by
downregulation of VEGF expression.
Key words
Vascular endothelial growth factor • Retinoic acid • Retinopathy
of prematurity
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