title: Protective effects of the neuropeptide PACAP in diabetic retinopathy.
abstract: Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide with highly potent neurotrophic and neuroprotective effects. PACAP and its receptors occur in the retina and PACAP has been applied in animal models of metabolic retinal disorders to reduce structural and functional damage. Furthermore, PACAP has been implicated as a potential anti-diabetic peptide. Our aim has been to investigate, by using a complex morphological, immunochemical and molecular biological approach, whether PACAP attenuates diabetic retinopathy. Diabetes was induced in rats with a single streptozotocin injection. PACAP was injected intravitreally into one eye (100 pmol) three times during the last week of a 3-week survival period. Retinas were processed for the following procedures: routine histology, immunohistochemistry (single and double labeling, whole-mount), quantitative reverse transcription with the polymerase chain reaction and Western blotting. Cone photoreceptors and dopaminergic amacrine and ganglion cells degenerated in diabetic retinas and glial fibrillary acidic protein were upregulated in Müller glial cells. The number of cones, the length of their outer segments and the cell number in the ganglion cell layer were decreased. PACAP ameliorated these structural changes. Moreover, PACAP increased the levels of PAC1-receptor and tyrosine-hydroxylase as detected by molecular biological methods. Thus, PACAP has significant protective effects in the diabetic retina. PACAP treatment attenuates neuronal cell loss in diabetic retinopathy, the protective effects of PACAP probably being mediated through the activation of PAC1-receptor. These results suggest that PACAP has a therapeutic potential in diabetic retinopathy.
authors.affiliation: Department of Experimental Zoology and Neurobiology, Institute of Biology, University of Pecs, Pecs, Hungary. kriszta.szabadfi@gmail.com
authors.forename: Krisztina
authors.initials: K
authors.lastname: Szabadfi
authors.forename: Tamas
authors.initials: T
authors.lastname: Atlasz
authors.forename: Peter
authors.initials: P
authors.lastname: Kiss
authors.forename: Dora
authors.initials: D
authors.lastname: Reglodi
authors.forename: Aliz
authors.initials: A
authors.lastname: Szabo
authors.forename: Krisztina
authors.initials: K
authors.lastname: Kovacs
authors.forename: Balint
authors.initials: B
authors.lastname: Szalontai
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Setalo
authors.forename: Eszter
authors.initials: E
authors.lastname: Banki
authors.forename: Katalin
authors.initials: K
authors.lastname: Csanaky
authors.forename: Andrea
authors.initials: A
authors.lastname: Tamas
authors.forename: Robert
authors.initials: R
authors.lastname: Gabriel
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000473:pathology; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000627:therapeutic use; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / Q000378:metabolism; D012160:Retina / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D017949:Retinal Cone Photoreceptor Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D020011:Protective Agents; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D014446:Tyrosine 3-Monooxygenase