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산소로 유도된 망막증 모델에서 트리암시놀론이 망막 혈관 관련 인자에 미치는 영향

Effect of Triamcinolone on Retinal Vessel-Related Factors in Oxygen-Induced Retinopathy Rats

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초록

목적: 트리암시놀론 아세토나이드(TA)의 Oxygen-induced retinopathy (OIR) 쥐 모델에서 혈관 관련 인자 및 혈관 누출에 대한 효과를알아보고자 한다. 대상과 방법: Sprague-Dawley계 흰쥐를 생후 2일부터 14일까지 고농도 산소에 노출한 후 생후 15일부터 30일까지 정상산소에 노출시켜 대조군과 비교하였다. TA (4 mg/kg) 2 μl를 생후 16일에 유리체내로 주입하였다. 망막 혈관 누출 현상은 Evans blue method를이용하였고 RT-PCR을 이용하여 혈관관련인자들의 mRNA 변화를 보았다. 결과: OIR 모델 흰쥐는 상대적 저산소로 인한 혈관누출이 나타났으며 TA을 주입하였을 때 혈관 투과성이 대조군에 비해 현저히 감소하였다. OIR 모델에서 HIF-1α, VEGF, SDF-1, ICAM-1의 mRNA 증가를 보였으며 TA 처리시 감소하였다. 또한 Occludin mRNA는 감소를보였으며 TA 처리시 증가하였다. 결론: OIR 모델에서 TA처리시 망막혈관누출의 감소를 보이며 이는 TA가 혈관누출억제에 작용하는 것으로 생각한다. 또한 허혈망막증에 증가하며 트리암시놀론 처리시 감소되는 것으로 이미 보고된 HIF-1α 및 VEGF 뿐만 아니라, SDF-1, ICAM-1, Occludin과 같은망막혈관 관련 인자에도 트리암시놀론이 작용하여 망막혈관파괴에 방지 효과가 있을 것으로 생각하며 추후 각 인자들의 단백질 변화를 통한 확인이 필요할 것이다.

Abstract

Purpose: The present study investigated the effects of triamcinolone acetonide (TA) on retinal vessel-related factors and retinal vascular leakage in the retina of oxygen-induced retinopathy (OIR) rats. Methods: Sprague-Dawley rats used for OIR were exposed to hyperoxia from postnatal day 2 to day 14, then returned to normoxia from day 15 to day 30 and compared with control rats. On postnatal day 16, 2 μl of TA (4 mg/kg) was injected into the vitreous of the right eye in control and OIR rats. The Evans blue method was used for evaluating vascular leakage and RT-PCR was performed for confirmation of mRNA expression. Results: In OIR rats exposed to hyperoxia, retinal vascular permeability increased when returned to normoxia. After intravitreal injection of TA, vascular permeability was decreased in OIR rats, but no changes were found in control rats. In OIR rats, mRNAs of HIF-1α, VEGF, SDF-1 and ICAM-1 were more expressed and down-regulated after intravitreal injection of TA. Occludin mRNA level was decreased in the hypoxic condition and up-regulated after TA treatment. Conclusions: The present study suggests the ability of TA to inhibit retinal vascular leakage in OIR rats and a possibility that TA controls expression of the HIF-1, VEGF, SDF-1, ICAM-1 and Occludin, which may protect retinal vascular destruction from hypoxic conditions; further studies are necessary to confirm changes in protein levels.

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