The Protective Effects of Endogenous PACAP in Oxygen-Induced Retinopathy

Kvarik, Timea; Reglődi, Dóra; Werling, Dora; Vaczy, Alexandra; Kovari, Petra; Szabó, Edina; Kovács, Krisztina; Hashimoto, Hitoshi; Ertl, Tibor; Gyarmati, J; Atlasz, Tamás

doi:10.1007/s12031-021-01846-2

Cited by 8 publications

(6 citation statements)

References 78 publications

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“…PACAP has well-documented neuro-and general cytoprotective effects, including protective actions in several retinopathies. Among others, PACAP has been shown to reduce injuries in models of retinopathy of prematurity, diabetic retinopathy, and retinopathies induced by inflammation, ischemia, neurotoxicity, and UV light [8,17,19,[21][22][23][27][28][29]. A difficulty of systemic treatment of retinopathies with PACAP is that the peptide has a short half-life in the serum due to the rapid degradation by the dipeptidyl-peptidase IV enzyme and that it is not known how it passes the blood-retina barrier.…”

Section: Discussionmentioning

confidence: 99%

“…Pituitary adenylate cyclase activating polypeptide (PACAP) is an endogenous neuropeptide first isolated as a hypothalamic peptide in two biologically active forms (PACAP1- [27][28][29][30][31][32][33][34][35][36][37][38]. It is the most conserved member of the secretin/glucagon/VIP family and it exerts diverse biological actions [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

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Retinoprotective Effects of PACAP Eye Drops in Microbead-Induced Glaucoma Model in Rats

Szabó

Patko

Vaczy

et al. 2021

IJMS

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Glaucoma is associated with increased intraocular pressure (IOP), causing the apoptosis of retinal ganglion cells (RGCs) and the loss of their axons leading to blindness. Pituitary adenylate cyclase activating polypeptide (PACAP) is neuroprotective in several neural injuries, including retinopathies. The aim of this study was to investigate the effects of PACAP1-38 eye drops in a model of glaucoma. IOP was elevated bilaterally by injections of microbeads to block the aqueous humor outflow. The control groups received the same volume of saline. Animals were treated with PACAP1-38 (1 µg/drop, 3 × 1 drop/day) or vehicle for 4 weeks starting one day after the injections. Retinal morphology by histology and optical coherence tomography, function by electroretinography, and IOP changes were analyzed. Animals were sacrificed 8 weeks after the injections. Microbeads injections induced a significant increase in the IOP, while PACAP1-38 treatment lowered it to normal levels (~10 mmHg). Significant retinal degeneration and functional impairment were observed in the microbead-injected group without PACAP1-38 treatment. In the microbeads + PACAP1-38 group, the retinal morphology and functionality were close to the normal values. In summary, our results show that PACAP1-38, given in form of eye drops, is neuroprotective in glaucoma, providing the basis for potential future therapeutic administration.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Retinoprotective Effects of PACAP Eye Drops in Microbead-Induced Glaucoma Model in Rats

Szabó

Patko

Vaczy

et al. 2021

IJMS

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“…Earlier it has been demonstrated that the melanopsin-containing retinal ganglion cells (which also express PACAP) are more resistant to degenerative processes, and this has raised the possibility of PACAP being involved in the endogenous protective machinery (La Morgia et al 2011). Indeed, we have shown that mice lacking PACAP have increased vulnerability in models of retinal ischemia and retinopathy of prematurity (Kvarik et al 2021;Szabad et al 2012). The retinal pigment epithelial cells, as the rst layer of the neural retina, play an important role in the photoprotection, metabolism, membrane renewal, vitamin A storage and growth factor supply of the photoreceptors.…”

Section: Discussionmentioning

confidence: 76%

Distribution of PACAP and PAC1 Receptor in the Human Eye

Patko

Szabó

Tóth

et al. 2022

Preprint

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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 the 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 the 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.

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“…Although some data indicate that PACAP may provoke inflammatory reactions in the rabbit eye (Wang et al 1997 ), most available data indicate that PACAP has very potent protective effects in the retina and cornea. For example, PACAP is protective in diabetic, ischemic, inflammatory retinopathies, in retinopathy of prematurity, in glaucoma (Atlasz et al 2010 ; Kvarik et al 2021 ; Maugeri et al 2019a ; Szabo et al 2021 ; Vaczy et al 2018 ), as well as traumatic and excitotoxic retinal injuries (Atlasz et al 2009 ; Seki et al 2008 ).…”

Section: Introductionmentioning

confidence: 99%

Distribution of PACAP and PAC1 Receptor in the Human Eye

et al. 2022

Self Cite

View full text Add to dashboard Cite

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.

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The Protective Effects of Endogenous PACAP in Oxygen-Induced Retinopathy

Cited by 8 publications

References 78 publications

Retinoprotective Effects of PACAP Eye Drops in Microbead-Induced Glaucoma Model in Rats

Retinoprotective Effects of PACAP Eye Drops in Microbead-Induced Glaucoma Model in Rats

Distribution of PACAP and PAC1 Receptor in the Human Eye

Distribution of PACAP and PAC1 Receptor in the Human Eye

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