Vascular endothelial growth factor is elevated in ocular fluids of eyes harbouring uveal melanoma: identification of a potential therapeutic window
Vascular endothelial growth factor is elevated in ocular fluids of eyes harbouring uveal melanoma: identification of a potential therapeutic window
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DOI：
10.1136/bjo.86.4.448
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发表时间：
2002-04-01
影响因子：
4.1
通讯作者：
Cree, IA
中科院分区：
文献类型：
--
作者：
Boyd, SR;Tan, D;Cree, IA
背景：葡萄膜黑色素瘤局部治疗的改进使许多患者有可能保留受影响的眼睛，但也有一部分患者会出现继发性并发症，如虹膜新生血管形成(NVI)，需要摘除眼球。尽管已知血管内皮生长因子A(VEGF-A)与新生血管生成相关，并可在实验模型中引起新生血管生成，但这种促血管生成的细胞因子在葡萄膜黑色素瘤中一直被报道缺失。目前抗血管内皮生长因子的新疗法正在进行临床试验，因此作者希望确定携带黑色素瘤的眼睛是否真的升高了。方法：分别检测了19只和30只眼摘除眼房水和玻璃体中的血管内皮生长因子-A浓度。结果：与常规白内障摘除手术的患者相比，携带黑色素瘤的眼睛中的血管内皮生长因子-A浓度升高(最高可达21.6 ng/ml)，均低于0.96 ng/ml。免疫组织化学显示，54%的眼虹膜和/或睫状体表达VEGF-A蛋白，82%的眼表达碱性成纤维细胞生长因子。在这些肿瘤中，只有9%的肿瘤在有限的范围内发现了血管内皮生长因子，而且水平非常低。房水或玻璃体中的血管内皮生长因子水平与视网膜脱离、肿瘤大小、血管密度或免疫组织化学均无明显相关性。虽然数量有限，但最高的血管内皮生长因子水平与既往的放射治疗以及虹膜或视神经头新生血管的存在有关。结论：基于这项研究，尽管葡萄膜黑色素瘤中的血管内皮生长因子的来源尚不清楚，但这些数据表明，抗血管内皮生长因子治疗可能在某些继发于葡萄膜黑色素瘤的新生血管生成的患者中发挥作用。
Background: Improved local treatment of uveal melanoma makes it possible for many patients to retain the affected eye, but a proportion will develop secondary complications such as neovascularisation of the iris (NVI) and require enucleation. Although vascular endothelial growth factor A (VEGF-A) is known to correlate with NVI and can cause NVI in experimental models, this pro-angiogenic cytokine is consistently reported to be absent in uveal melanoma. Novel anti-VEGF therapies are now in clinical trial, and the authors therefore wished to determine whether VEGF-A was indeed elevated in melanoma bearing eyes.Methods: VEGF-A concentrations were measured in aqueous and vitreous from 19 and 30 enucleated eyes respectively.Results: Elevated VEGF-A concentrations (up to 21.6 ng/ml) were found in melanoma bearing eyes compared with samples from patients undergoing routine cataract extraction (all had values below 0.96 ng/ml). Immunohistochemistry showed VEGF-A protein in the iris and/or ciliary body of 54% and basic fibroblast growth factor (bFGF) in 82% of the eyes examined. VEGF was found to a limited extent and at very low levels in only 9% of these tumours. Aqueous or vitreous VEGF levels showed no apparent correlation with retinal detachment, tumour size, vascularity, or immunohistochemistry. Though limited in number, the highest VEGF levels correlated with previous radiation therapy, and with the presence neovascularisation of the iris or optic nerve head. bFGF was not significantly elevated in ocular fluids: it is known to be a pro-angiogenic agent and was detected in the majority of primary uveal melanomas.Conclusion: Based on this study, though the source of VEGF within eyes harbouring uveal melanoma is not clear, these data suggest that anti-VEGF therapy might prove useful in the management of some patients with NVI secondary to uveal melanoma.