Passage through the ocular barriers and beneficial effects in retinal ischemia of topical application of PACAP1-38 in rodents

Dora Werling, William A. Banks, Therese S. Salameh, Timea Kvarik, Laszloakos Kovacs, Alexandra Vaczy, Edina Szabo, Flora Mayer, Rita Varga, A. Tamás, G. Tóth, Zsolt Biro, Tamas Atlasz, D. Reglodi

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10 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number675
JournalInternational Journal of Molecular Sciences
Volume18
Issue number3
DOIs
Publication statusPublished - Mar 21 2017

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Keywords

  • Carotid artery occlusion
  • Eye drops
  • Ischemic retinopathy
  • Neuroprotection
  • PACAP

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Computer Science Applications
  • Spectroscopy
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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