title: Pituitary Adenylate Cyclase Activating Polypeptide, A Potential Therapeutic Agent for Diabetic Retinopathy in Rats: Focus on the Vertical Information Processing Pathway.
abstract: Pituitary adenylate cyclase activating polypeptide (PACAP) is a neurotrophic and neuroprotective peptide that has been shown to exert protective effects in different neuronal injuries, such as retinal degenerations. Diabetic retinopathy (DR), the most common complication of diabetes, affects the microvasculature and neuronal architecture of the retina. We have proven earlier that PACAP is also protective in a rat model of DR. In this study, streptozotocin-induced DR was treated with intravitreal PACAP administration in order to further analyze the synaptic structure and proteins of PACAP-treated diabetic retinas, primarily in the vertical information processing pathway. Streptozotocin-treated Wistar rats received intravitreal PACAP injection three times into the right eye 2 weeks after the induction of diabetes. Morphological and molecular biological (qRT-PCR; Western blot) methods were used to analyze retinal synapses (ribbons, conventional) and related structures. Electron microscopic analysis revealed that retinal pigment epithelium, the ribbon synapses and other synaptic profiles suffered alterations in diabetes. However, in PACAP-treated diabetic retinas more bipolar ribbon synapses were found intact in the inner plexiform layer than in DR animals. The ribbon synapse was marked with C-terminal binding protein 2/Bassoon and formed horseshoe-shape ribbons, which were more retained in PACAP-treated diabetic retinas than in DR rats. These results are supported by molecular biological data. The selective degeneration of related structures such as bipolar and ganglion cells could be ameliorated by PACAP treatment. In summary, intravitreal administration of PACAP may have therapeutic potential in streptozotocin-induced DR through maintaining synapse integrity in the vertical pathway.
authors.affiliation: Departments of Experimental Zoology and Neurobiology, University of Pecs, Pecs, Hungary.|Janos Szentagothai Research Centre, University of Pecs, Pecs, Hungary.
authors.forename: K
authors.initials: K
authors.lastname: Szabadfi
authors.affiliation: Janos Szentagothai Research Centre, University of Pecs, Pecs, Hungary. dora.reglodi@aok.pte.hu.|Department of Anatomy, MTA-PTE PACAP Lendulet Research Group, University of Pecs, Szigeti u. 12., Pecs, 7624, Hungary. dora.reglodi@aok.pte.hu.
authors.forename: D
authors.initials: D
authors.lastname: Reglodi
authors.affiliation: Biochemistry and Medical Chemistry, University of Pecs, Pecs, Hungary.
authors.forename: A
authors.initials: A
authors.lastname: Szabo
authors.affiliation: Departments of Experimental Zoology and Neurobiology, University of Pecs, Pecs, Hungary.|Janos Szentagothai Research Centre, University of Pecs, Pecs, Hungary.
authors.forename: B
authors.initials: B
authors.lastname: Szalontai
authors.affiliation: Departments of Experimental Zoology and Neurobiology, University of Pecs, Pecs, Hungary.|Janos Szentagothai Research Centre, University of Pecs, Pecs, Hungary.
authors.forename: A
authors.initials: A
authors.lastname: Valasek
authors.affiliation: Medical Biology, University of Pecs, Pecs, Hungary.
authors.forename: Gy
authors.initials: G
authors.lastname: Setalo
authors.affiliation: Department of Anatomy, MTA-PTE PACAP Lendulet Research Group, University of Pecs, Szigeti u. 12., Pecs, 7624, Hungary.
authors.forename: P
authors.initials: P
authors.lastname: Kiss
authors.affiliation: Department of Anatomy, MTA-PTE PACAP Lendulet Research Group, University of Pecs, Szigeti u. 12., Pecs, 7624, Hungary.
authors.forename: A
authors.initials: A
authors.lastname: Tamas
authors.affiliation: Sport Sciences and Physical Education, University of Pecs, Pecs, Hungary.
authors.forename: M
authors.initials: M
authors.lastname: Wilhelm
authors.affiliation: Departments of Experimental Zoology and Neurobiology, University of Pecs, Pecs, Hungary.|Janos Szentagothai Research Centre, University of Pecs, Pecs, Hungary.
authors.forename: R
authors.initials: R
authors.lastname: Gabriel
mesh_terms: D000818:Animals; D003930:Diabetic Retinopathy / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology* / Q000517:prevention & control; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D010786:Photoreceptor Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure*; D051245:Retinal Bipolar Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D055213:Retinal Pigment Epithelium / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D013311:Streptozocin; D013569:Synapses / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D018696:Neuroprotective Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D013311:Streptozocin
keywords: Bipolar cells; Ganglion cells; Photoreceptors; Retinal pigment epithelium; Ribbon synapses