Distribution of PACAP and PAC1 Receptor in the Human Eye

Abstract

Pituitary adenylate cyclase–activating polypeptide (PACAP) is a neuropeptide with widespread distribution and diverse biological functions. Several studies show that PACAP has strong cytoprotective effects mediated mostly through its specific PAC1 receptor (PAC1-R) and it plays important roles in several pathological conditions. Its distribution and altered expression are known in various human tissues, but there is no descriptive data about PACAP and its receptors in the human eyebulb. Since PACAP38 is the dominant form of the naturally occurring PACAP, our aim was to investigate the distribution of PACAP38-like immunoreactivity in the human eye and to describe the presence of PAC1-R. Semiquantitative evaluation was performed after routine histology and immunohistochemical labeling on human eye sections. Our results showed high level of immunopositivity in the corneal epithelium and endothelium. Within the vascular layer, the iris and the ciliary body had strong immunopositivity for both PACAP and PAC1-R. Several layers of the retina showed immunoreactivity for PACAP and PAC1-R, but the ganglion cell layer had a special pattern in the immunolabeling. Labeling was observed in the neuropil within the optic nerve in both cases and glial cells displayed immunoreactivity for PAC1-R. In summary, our study indicates the widespread occurrence of PACAP and its specific receptor in the human eye, implying that the results from in vitro and animal studies have translational value and most probably are also present in the human eye.

Investigation of PACAP38 and PAC1 Receptor Expression in Human Retinoblastoma and the Effect of PACAP38 Administration on Human Y-79 Retinoblastoma Cells

“…In the first part of our study, we analyzed human enucleation specimens removed because of retinoblastoma for PACAP38 and PAC1R immunostaining and described, for the first time, the distribution of PACAP38 and PAC1R expression in human retinoblastoma. We found PACAP38 and PAC1R immunopositivity in the tumor-free area of the eyes consistent with the results of the first description of the distribution of PACAP38 and PAC1R in the human eye [30] which, therefore, served as a positive internal control. In retinoblastoma, we observed only focal, perinuclear dot-like immunopositivity for both PACAP38 and PAC1R.…”

“…Table 1 provides an overview of the primary demographic and clinical features, while Table 2 summarizes the main pathological findings of the cases. In accordance with our earlier observations [30], we found PACAP38 and PAC1R immunopositivity in disease-free areas of the eye, including the cornea (both epithelial and endothelial cells), the iris (stroma and muscles), the ciliary body, and different retinal layers (pigment epithelial layer, inner plexiform layer, and ganglion cell layer). These findings served as a positive internal control.…”

“…The inner plexiform layer had strong PACAP38 and PAC1R immunoreactivity. Interestingly, a specific staining pattern was observed in the ganglion cell layer, where some ganglion cells showed very strong, and others showed negative, immunosignals [30]. PACAP takes part in a wide range of physiological [31][32][33] and pathological processes [34,35].…”

“…Additionally, from retinal homogenates obtained from human fetuses, they successfully identified the mRNA for both PACAP and its receptors. The first detailed exploration of the distribution of PACAP38 and PAC1R within the normal human eye was conducted in 2022 [30]. Corneal epithelial and endothelial cells, the iris (both muscle and stroma), the ciliary body, several retinal layers, and the optic nerve showed immunopositivity for both PACAP38 and PAC1R.…”

Involvement of Vasoactive Intestinal Peptide Family Members in Diabetic Keratopathy

“…Moreover, it exerts an important role in reproduction, pregnancy, early development, and aging [125][126][127][128][129][130][131]. In the eye, PACAP and its high-affinity receptor PAC1 are expressed in the retinal layers [132][133][134][135][136][137], in the ciliary body, in the optic nerve, in the conjunctiva, and in the iris [50,133,138]. Moreover, the expression of PACAP and its receptors has been largely demonstrated in the cornea.…”