The effect of thalidomide on neovascularization in a mouse model of retinopathy of prematurity |
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Authors: | Ronen Rabinowitz Gabriel Katz Mordechai Rosner Sara Pri-Chen Abraham Spierer |
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Institution: | (1) Goldschleger Eye Institute, Sheba Medical Center, Tel-Hashomer, Israel;(2) Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel;(3) Ahdut Haavoda 11 Str., Givataim, 53205, Israel |
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Abstract: | Purpose Abnormal angiogenesis is the hallmark feature of retinopathy of prematurity (ROP), and contributes to the severe visual loss
that accompanies this disease. Thalidomide is a well-known anti-angiogenic drug. We tested the assumption that injection of
intraperitoneal thalidomide could reduce the severity of oxygen-induced retinopathy (OIR) in a mouse model.
Methods Forty-three baby wild type mice were used in this study. The mouse model of oxygen-induced retinopathy consisted of a 5-day
exposure to 75% oxygen from postnatal day 7 to 12 (P12) followed by 5 days in room air (relative hypoxia). Control mice were
those with normally developing retinal vasculature exposed to room air from birth until postnatal day 17 (P17). Thalidomide
(200 mg/Kg) was administered daily intraperitoneally to control and ROP mice in two protocols: (1) from P12 to P16, and (2)
from P11 to P15 . Fluorescein-conjugated dextran angiography of retinal vasculature was performed on P17, and retinal whole
mounts were prepared to score features of retinopathy. The parameters that were scored in a masked fashion included blood
vessel growth, blood vessel tufts formation, extra retinal neovascularization, degree of central constriction, and tortuosity
of vessels. These parameters constitute the Modified Retinopathy Scoring System (MRSS). In addition, quantification of the
number of blood vessel tufts was performed in a masked fashion with hematoxylin & eosin (H&S) staining of paraffin-embedded
eye sections.
Results The retinopathy score by MRSS in the thalidomide treated mice was similar to that of untreated mice that were exposed to oxygen
(9.3 ± 1.9 vs 10.15 ± 1.6; p = 0.21). The neovascularization count was also similar between the two groups (10.4 ± 5.6 vs 9.6 ± 4.8; p = 0.56). In the control group left in the room air, the retinopathy score was 0.19 ± 0.37 (p = 0) and the neovascularization count was also very low (2.92 ± 2.14; p = 0).
Conclusions Although thalidomide might have a proven anti-angiogenic and anti-inflammatory effect, our model did not show a significant
effect on the retinopathy. The reason might be an ineffective level of the drug in the retina due to ineffective metabolism
of the drug, or due to blockage of the drug by the blood-retina barrier, or the involvement of other factors besides those
influenced by thalidomide in the process.
Poster presented at ISOPT, Berlin 2006. |
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Keywords: | Thalidomide Neovascularization Retinopathy of prematurity Mouse Oxygen-induced retinopathy Angiogenesis |
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