title: Ocular Delivery of PACAP1-27 Protects the Retina From Ischemic Damage in Rodents.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  PACAP1-27, delivered in the SOCB vehicle as eye drops, was retinoprotective in ischemic retinopathy, providing the basis for future therapeutic administration.
authors.affiliation: Department of Anatomy, University of Pecs, Pecs, Hungary 2Department of Ophthalmology, University of Pecs, Pecs, Hungary.
authors.forename: Dora
authors.initials: D
authors.lastname: Werling
authors.affiliation: Department of Anatomy, University of Pecs, Pecs, Hungary.
authors.forename: Dora
authors.initials: D
authors.lastname: Reglodi
authors.affiliation: Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Washington, United States 4Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, Washington, United States.
authors.forename: William A
authors.initials: WA
authors.lastname: Banks
authors.affiliation: Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Washington, United States 4Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, Washington, United States.
authors.forename: Therese S
authors.initials: TS
authors.lastname: Salameh
authors.affiliation: Department of Biochemistry and Medical Chemistry, University of Pecs, Pecs, Hungary.
authors.forename: Krisztina
authors.initials: K
authors.lastname: Kovacs
authors.affiliation: Department of Anatomy, University of Pecs, Pecs, Hungary.
authors.forename: Timea
authors.initials: T
authors.lastname: Kvarik
authors.affiliation: Department of Anatomy, University of Pecs, Pecs, Hungary.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Vaczy
authors.affiliation: Department of Anatomy, University of Pecs, Pecs, Hungary.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Kovacs
authors.affiliation: Department of Anatomy, University of Pecs, Pecs, Hungary.
authors.forename: Flora
authors.initials: F
authors.lastname: Mayer
authors.affiliation: Department of Anatomy, University of Pecs, Pecs, Hungary.
authors.forename: Bese
authors.initials: B
authors.lastname: Danyadi
authors.affiliation: Department of Anatomy, University of Pecs, Pecs, Hungary.
authors.forename: Emese
authors.initials: E
authors.lastname: Lokos
authors.affiliation: Department of Anatomy, University of Pecs, Pecs, Hungary.
authors.forename: Andrea
authors.initials: A
authors.lastname: Tamas
authors.affiliation: Department of Medical Chemistry, University of Szeged, Szeged, Hungary.
authors.forename: Gabor
authors.initials: G
authors.lastname: Toth
authors.affiliation: Department of Ophthalmology, University of Pecs, Pecs, Hungary.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Biro
authors.affiliation: Department of Anatomy, University of Pecs, Pecs, Hungary 7Department of Sportbiology, University of Pecs, Pecs, Hungary 8Janos Szentagothai Research Center, University of Pecs, Pecs, Hungary.
authors.forename: Tamas
authors.initials: T
authors.lastname: Atlasz
mesh_terms: D000818:Animals; D015153:Blotting, Western; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D063928:Ependymoglial Cells / Q000473:pathology; D007150:Immunohistochemistry; D007511:Ischemia / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy; D008297:Male; D051379:Mice; D018377:Neurotransmitter Agents / Q000008:administration & dosage; D009883:Ophthalmic Solutions; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000187:drug effects* / Q000473:pathology; D012162:Retinal Degeneration / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D012171:Retinal Vessels / Q000187:drug effects / Q000473:pathology*
chemical_list: D016207:Cytokines; D018377:Neurotransmitter Agents; D009883:Ophthalmic Solutions; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide