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. OZER<sup>2

1</sup>Department 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