Spatiotemporal Expression Changes of PACAP and Its Receptors in Retinal Ganglion Cells After Optic Nerve Crush

Pituitary adenylate cyclase-activating polypeptide (PACAP) has been demonstrated to play a crucial part in protecting retinal ganglion cells (RGCs) from apoptosis in various retinal injury animal models. PACAP has two basic groups of receptors: PACAP receptor type 1 (PAC1R) and vasoactive intestinal polypeptide/PACAP receptors (VPAC1R and VPAC2R). However, few studies illustrated the spatial and temporal expression changes of endogenous PACAP and its receptors in a rodent optic nerve crush (ONC) model. In this study, a significant upregulation of PACAP and PAC1R in the retina after ONC was observed in both protein and RNA levels. The peak level of PACAP and PAC1R expression could be found on the fifth day following ONC. In addition, immunofluorescent labeling indicated that PACAP and PAC1R were localized mainly in RGCs. On the contrary, VPAC1R and VPAC2R were hardly detected in the retina. Collectively, the spatiotemporal expression of PACAP and its high-affinity receptor PAC1R were remarkably changed after ONC, and mainly expressed in the ganglion cell layer of the retina. This suggested that the upregulation of PACAP and PAC1R may play a vital role in RGC death after ONC.