The Neuroprotective Peptide PACAP1-38 Contributes to Horizontal Cell Development in Postnatal Rat Retina
| Autor: | Monika Lakk, Gergely Berta, Viktoria Denes, Peter Geck, Zsolt Nyisztor, Zoltan Godri, Robert Gábriel, Orsolya Hideg |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Calbindins Cellular differentiation Blotting Western Gene Expression Cell Count Biology Retinal Horizontal Cells Real-Time Polymerase Chain Reaction Calbindin Retina 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Animals Rats Wistar Receptor Growth Substances Mitosis Cell Proliferation Microscopy Confocal Retinoblastoma Cell growth Retinal Cell Differentiation medicine.disease Cell biology Rats 030104 developmental biology medicine.anatomical_structure chemistry Pituitary Adenylate Cyclase-Activating Polypeptide Female 030217 neurology & neurosurgery Receptors Pituitary Adenylate Cyclase-Activating Polypeptide Type I |
| Zdroj: | Investigative ophthalmologyvisual science. 60(2) |
| ISSN: | 1552-5783 |
| Popis: | Purpose PACAP1-38, a member of the secretin/glucagon superfamily, is expressed in the developing retina with documented neuroprotective effects. However, its function in retinal cell differentiation has yet to be elucidated. Our goals, therefore, were to identify PAC1 expressing cells morphologically, investigate the PACAP1-38 action functionally, and establish PACAP1-38 regulated events developmentally during the first postnatal week in rat retina. Methods P1 retinal sections or whole mounts of Wistar rats were used to reveal PAC1 and calbindin immunoreactive structures. P1, P3, or P7 pups were injected intravitreally with 100 pmol PACAP1-38. Tissues were harvested 24 hours post-treatment, then processed for calbindin immunohistochemistry to determine horizontal cell number, or 6, 12, 24 hours post-treatment for real-time PCR and immunoblots to detect PCNA expression. To localize proliferating cells, anti-PCNA antibody was applied. Results We showed various PAC1 expressing cells in RPE, NBL, and GCL in P1 retina including calbindin positive horizontal cells. We found that PACAP1-38 induced a marked cell number increase at P3 and P7 and showed upregulated cell proliferation as its mechanism; however, it was ineffective at P1. PACAP1-38 induced proliferative cells localized in the NBL, and double-marker studies demonstrated that the induced proliferative cells were horizontal cells. Conclusions PACAP1-38 appears to act in retinal differentiation by inducing mitosis selectively in a time and cell specific manner through PAC1. The control of horizontal cell proliferation raises the novel possibilities that (1) PACAP1-38 may be a major player in retinal patterning and (2) PACAP signaling may be critical in retinoblastoma. |
| Databáze: | OpenAIRE |
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