TY - CHAP AU - Atlasz, Tamás AU - Váczy, Alexandra AU - Werling, Dóra AU - Kiss, Péter AU - Tamás, Andrea AU - Kovács, Krisztina AU - Fábián, Eszter AU - Kvárik, Tímea AU - Mammel, Barbara AU - Dányádi, Bese AU - Lőkös, Emese AU - Reglődi, Dóra ED - Reglődi, Dóra ED - Tamás, Andrea TI - Protective Effects of PACAP in the Retina T2 - Pituitary Adenylate Cyclase Activating Polypeptide — PACAP PB - Springer Netherlands CY - Cham SN - 9783319351353 T3 - Current Topics in Neurotoxicity, ISSN 2363-9563 ; 11. PY - 2016 SP - 501 EP - 527 PG - 27 DO - 10.1007/978-3-319-35135-3_30 UR - https://m2.mtmt.hu/api/publication/3134694 ID - 3134694 LA - English DB - MTMT ER - TY - JOUR AU - Werling, Dóra AU - Reglődi, Dóra AU - Banks, William A AU - Salameh, Theresa S AU - Kovács, Krisztina AU - Kvárik, Tímea AU - Váczy, Alexandra AU - Kovács, László Ákos AU - Mayer, Flora AU - Dányádi, Bese AU - Lőkös, Emese AU - Tamás, Andrea AU - Tóth, Gábor AU - Biró, Zsolt AU - Atlasz, Tamás TI - Ocular delivery of PACAP1-27 protects the retina from ischemic damage in rodents JF - INVESTIGATIVE OPHTHALMOLOGY AND VISUAL SCIENCE J2 - INVEST OPHTH VIS SCI VL - 57 PY - 2016 IS - 15 SP - 6683 EP - 6691 PG - 9 SN - 0146-0404 DO - 10.1167/iovs.16-20630 UR - https://m2.mtmt.hu/api/publication/3127952 ID - 3127952 AB - Purpose: Pituitary adenylate cyclase activating polypeptide (PACAP) is neuroprotective in neuronal injuries. Bilateral common carotid artery occlusion (BCCAO) causes chronic hypoperfusion-induced degeneration in the rat retina, where we proved the retinoprotective effect of intravitreal PACAP. Although this route of administration is a common clinical practice in several diseases, easier routes are clinically important. Our aim was to investigate the potential retinoprotective effects of PACAP eye drops in BCCAO-induced ischemic retinopathy. Methods: After performing BCCAO in rats, the right eyes were treated with PACAP1-27 eye drops (1 μg/drop, 2 × 1 drops/day for 5 days), containing different vehicles: saline, water for injections, thiomersal or benzalkonium solution for ophthalmic use (SOCB). Histology and immunohistochemistry were performed 2 weeks after surgery, while molecular analysis was performed 24 hours after BCCAO. Passage of PACAP1-27 through the ocular layers was tested with radioactive PACAP-SOCB in mice. Results: Bilateral common carotid artery occlusion led to a severe degeneration of all retinal layers. Solution for ophthalmic use was the most effective vehicle for delivering PACAP (PACAP-SOCB), significantly ameliorating BCCAO-induced damage. The massive upregulation of GFAP was not observed in retinas treated with PACAP-SOCB eye drops. PACAP-SOCB treatment also increased activation of the protective Akt and ERK1/2 in hypoperfused retinas. The cytokine profile showing upregulation in different cytokines was attenuated by PACAP-SOCB. Radioactive PACAP reached the retina when delivered in SOCB-containing eye drops. Conclusions: PACAP1-27, delivered in the SOCB vehicle as eye drops, was retinoprotective in ischemic retinopathy, providing the basis for future therapeutic administration. LA - English DB - MTMT ER - TY - JOUR AU - Váczy, Alexandra AU - Reglődi, Dóra AU - Somoskeoy, T AU - Kovács, Krisztina AU - Lőkös, Emese AU - Szabó, Edina AU - Tamás, Andrea AU - Atlasz, Tamás TI - The Protective Role of PAC1-Receptor Agonist Maxadilan in BCCAO-Induced Retinal Degeneration JF - JOURNAL OF MOLECULAR NEUROSCIENCE J2 - J MOL NEUROSCI VL - 60 PY - 2016 IS - 2 SP - 186 EP - 194 PG - 9 SN - 0895-8696 DO - 10.1007/s12031-016-0818-4 UR - https://m2.mtmt.hu/api/publication/3105000 ID - 3105000 AB - A number of studies have proven that pituitary adenylate cyclase activating polypeptide (PACAP) is protective in neurodegenerative diseases. Permanent bilateral common carotid artery occlusion (BCCAO) causes severe degeneration in the rat retina. In our previous studies, protective effects were observed with PACAP1-38, PACAP1-27, and VIP but not with their related peptides, glucagon, or secretin in BCCAO. All three PACAP receptors (PAC1, VPAC1, VPAC2) appear in the retina. Molecular and immunohistochemical analysis demonstrated that the retinoprotective effects are most probably mainly mediated by the PAC1 receptor. The aim of the present study was to investigate the retinoprotective effects of a selective PAC1-receptor agonist maxadilan in BCCAO-induced retinopathy. Wistar rats were used in the experiment. After performing BCCAO, the right eye was treated with intravitreal maxadilan (0.1 or 1 muM), while the left eye was injected with vehicle. Sham-operated rats received the same treatment. Two weeks after the operation, retinas were processed for standard morphometric and molecular analysis. Intravitreal injection of 0.1 or 1 muM maxadilan caused significant protection in the thickness of most retinal layers and the number of cells in the GCL compared to the BCCAO-operated eyes. In addition, 1 muM maxadilan application was more effective than 0.1 muM maxadilan treatment in the ONL, INL, IPL, and the entire retina (OLM-ILM). Maxadilan treatment significantly decreased cytokine expression (CINC-1, IL-1alpha, and L-selectin) in ischemia. In summary, our histological and molecular analysis showed that maxadilan, a selective PAC1 receptor agonist, has a protective role in BCCAO-induced retinal degeneration, further supporting the role of PAC1 receptor conveying the retinoprotective effects of PACAP. LA - English DB - MTMT ER -