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PACAP-ADNP轴通过干扰从视网膜色素表皮细胞分泌的VEGF来防止外视网膜屏障的分解和胆管新血管化

Agata Grazia D'Amico¹, Grazia Maugeri², Benedetta Magrì²

¹Department of Drug and Health Sciences, Section of System Biology, University of Catania, 95125 Catania, Italy.

|July 26, 2023

概括

该PACAP-ADNP通路保护外血液视网膜屏障免受损伤,并通过抵消VEGF的影响来抑制糖尿病视网膜病变中异常的血管生长.

科学领域:

眼科医生眼科眼科
细胞生物学细胞生物学
分子医学是分子医学.

背景情况:

糖尿病视网膜病变 (DR) 涉及视网膜代谢变化,包括RPE缺氧和VEGF过度表达.
VEGF损害了外血液视网膜屏障 (oBRB) 的完整性,并促进胆道新血管化.
该oBRB调节视网膜微环境,其损伤是DR进展的核心.

研究的目的:

研究PACAP-ADNP轴对糖尿病视网膜病变中的oBRB损伤的保护作用.
为了确定PACAP-ADNP轴是否可以控制VEGF诱导的冠状腺新血管化.
在糖尿病模型中验证ADNP表达及其对oBRB完整性的参与.

主要方法:

在STZ诱导的糖尿病动物中评估ADNP表达.
使用的ARPE-19细胞暴露在高血糖/低毒的侮辱中,以产生带有VEGF的条件介质 (CM).
在ARPE细胞单层上使用跨表皮电阻和透性试验评估了oBRB完整性.
分析了紧结蛋白 (ZO-1,ocludin) 的表达.
评估了PACAP-ADNP轴对CM培养的H5V内皮细胞中血管状结构形成的影响.

主要成果:

在STZ诱导的糖尿病动物中证实了ADNP表达.
已经证明,PACAP-ADNP轴通过保护紧密结合蛋白来保持oBRB的完整性.
PACAP-ADNP轴抵消了内皮细胞中VEGF诱导的血管状结构的形成.
在PACAP-ADNP信号中,对oBRB的损伤得到了缓解.

结论:

在糖尿病视网膜病变期间,PACAP-ADNP轴在预防oBRB损伤方面发挥着至关重要的作用.
这一途径有效地控制了由VEGF引起的异常冠状腺新血管化.
PACAP-ADNP代表了治疗糖尿病视网膜病变并发症的潜在治疗标.

关键词:

过高糖血症是什么意思氧气过低,VEGFF的使用情况外部的血液视网膜屏障.这就是PacaPap的意义.

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