Werling Dora, Banks William A, Salameh Therese S, Kvarik Timea, Kovacs Laszlo Akos, Vaczy Alexandra, Szabo Edina, Mayer Flora, Varga Rita, Tamas Andrea, Toth Gabor, Biro Zsolt, Atlasz Tamas, Reglodi Dora
Department of Anatomy, University of Pecs, Medical School, Pecs 7624, Hungary.
Department of Ophthalmology, University of Pecs, Pecs 7624, Hungary.
Int J Mol Sci. 2017 Mar 21;18(3):675. doi: 10.3390/ijms18030675.
The neuropeptide pituitary adenylate cyclase activating polypeptide (PACAP) has two active forms, PACAP1-27 and PACAP1-38. Among the well-established actions are PACAP's neurotrophic and neuroprotective effects, which have also been proven in models of different retinopathies. The route of delivery is usually intravitreal in studies proving PACAP's retinoprotective effects. Recently, we have shown that PACAP1-27 delivered as eye drops in benzalkonium-chloride was able to cross the ocular barriers and exert retinoprotection in ischemia. Since PACAP1-38 is the dominant form of the naturally occurring PACAP, our aim was to investigate whether the longer form is also able to cross the barriers and exert protective effects in permanent bilateral common carotid artery occlusion (BCCAO), a model of retinal hypoperfusion. Our results show that radioactive PACAP1-38 eye drops could effectively pass through the ocular barriers to reach the retina. Routine histological analysis and immunohistochemical evaluation of the Müller glial cells revealed that PACAP1-38 exerted retinoprotective effects. PACAP1-38 attenuated the damage caused by hypoperfusion, apparent in almost all retinal layers, and it decreased the glial cell overactivation. Overall, our results confirm that PACAP1-38 given in the form of eye drops is a novel protective therapeutic approach to treat retinal diseases.
神经肽垂体腺苷酸环化酶激活多肽（PACAP）有两种活性形式，即PACAP1 - 27和PACAP1 - 38。PACAP的神经营养和神经保护作用是其已被充分证实的作用，在不同视网膜病变模型中也得到了验证。在证明PACAP视网膜保护作用的研究中，给药途径通常是玻璃体内注射。最近，我们发现以含有苯扎氯铵的眼药水形式给药的PACAP1 - 27能够穿过眼屏障并在缺血时发挥视网膜保护作用。由于PACAP1 - 38是天然存在的PACAP的主要形式，我们的目的是研究这种较长形式是否也能够穿过屏障并在永久性双侧颈总动脉闭塞（BCCAO）模型（一种视网膜灌注不足模型）中发挥保护作用。我们的结果表明，放射性PACAP1 - 38眼药水能够有效穿过眼屏障到达视网膜。对 Müller 胶质细胞的常规组织学分析和免疫组化评估显示，PACAP1 - 38发挥了视网膜保护作用。PACAP1 - 38减轻了灌注不足造成的损伤，这种损伤在几乎所有视网膜层都很明显，并且它减少了胶质细胞的过度激活。总体而言，我们的结果证实，以眼药水形式给药的PACAP1 - 38是一种治疗视网膜疾病的新型保护性治疗方法。
