Effects of cyclopeptide C*HSDGIC* from the cyclization of PACAP (1-5) on the proliferation and UVB-induced apoptosis of the retinal ganglion cell line RGC-5

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide that confers potent neurotrophic and neuroprotective effects. Cyclopeptide C*HSDGIC* (CHC), which results from the cyclization of PACAP (1-5) with disulfide, has been demonstrated to represent a potent agonist for the PACAP-specific receptor PAC1 which mediates the majority of PACAP's effects. In this study, the expression of PAC1 in a rat retinal ganglion cell line (RGC-5) was confirmed using a western blot analysis, and it was determined that CHC promoted the proliferation of RGC-5 cells using the cell counting kit-8 (CCK8) assay and flow cytometry. Furthermore, the treatment of CHC attenuated the decrease of cell viability in cells exposed to UVB irradiation. Flow cytometry and a JC-1 assay revealed that the CHC treatment protected the RGC-5 cells against UVB-induced apoptosis. In addition, similar to PACAP, the anti-apoptotic effect of CHC was related to the down-regulation of caspase-3. In summary, these results demonstrate for the first time that PAC1 is present in RGC-5 cells and that CHC, a cyclopeptide from PACAP, promotes RGC-5 cell proliferation and attenuates UVB-induced apoptosis.