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

Szabó, Edina; Patko, Evelin; Vaczy, Alexandra; Molitor, D. L.; Csutak, Adrienne; Tóth, Gábor; Reglődi, Dóra; Atlasz, Tamás

doi:10.3390/ijms22168825

Cited by 16 publications

(21 citation statements)

References 53 publications

(83 reference statements)

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“…Furthermore, PACAP and its receptors have also been shown to act on chloride channels, which are essential in the production of aqueous humour, independently from the cAMP pathway (Alsha e et al 2014; Derand et al 2004;Leung et al 2001;Martinez-Rojas et al 2021). The role of PACAP has been implied not only in the production, but also in the absorption of the aqueous humour, as our most recent data have provided evidence that PACAP treatment leads to reduced intraocular pressure in a rat model of glaucoma (Szabo et al 2021).…”

Section: Discussionmentioning

confidence: 98%

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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Section: Discussionmentioning

confidence: 98%

Distribution of PACAP and PAC1 Receptor in the Human Eye

Patko

Szabó

Tóth

et al. 2022

Preprint

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“…Eye drops can potentially be utilized as a non-invasive option but this method also suffers from the presence of barriers ( Werling et al, 2017 ). However, eye drops have already been successfully implemented as a method of delivery, including the usage of PACAP against glaucoma ( Szabo et al, 2021 ) and SST against DR ( Hernández et al, 2013 ). While intraocular injections offer a direct solution to the problem of permeability, their invasive nature makes them dangerous as the adverse effects of repeated injections (inflammation, retinal detachment) can have severe consequences on retinal health.…”

Section: Discussionmentioning

confidence: 99%

Relevance of Peptide Homeostasis in Metabolic Retinal Degenerative Disorders: Curative Potential in Genetically Modified Mice

et al. 2022

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The mammalian retina contains approximately 30 neuropeptides that are synthetized by different neuronal cell populations, glia, and the pigmented epithelium. The presence of these neuropeptides leaves a mark on normal retinal molecular processes and physiology, and they are also crucial in fighting various pathologies (e.g., diabetic retinopathy, ischemia, age-related pathologies, glaucoma) because of their protective abilities. Retinal pathologies of different origin (metabolic, genetic) are extensively investigated by genetically manipulated in vivo mouse models that help us gain a better understanding of the molecular background of these pathomechanisms. These models offer opportunities to manipulate gene expression in different cell types to help reveal their roles in the preservation of retinal health or identify malfunction during diseases. In order to assess the current status of transgenic technologies available, we have conducted a literature survey focused on retinal disorders of metabolic origin, zooming in on the role of retinal neuropeptides in diabetic retinopathy and ischemia. First, we identified those neuropeptides that are most relevant to retinal pathologies in humans and the two clinically most relevant models, mice and rats. Then we continued our analysis with metabolic disorders, examining neuropeptide-related pathways leading to systemic or cellular damage and rescue. Last but not least, we reviewed the available literature on genetically modified mouse strains to understand how the manipulation of a single element of any given pathway (e.g., signal molecules, receptors, intracellular signaling pathways) could lead either to the worsening of disease conditions or, more frequently, to substantial improvements in retinal health. Most attention was given to studies which reported successful intervention against specific disorders. For these experiments, a detailed evaluation will be given and the possible role of converging intracellular pathways will be discussed. Using these converging intracellular pathways, curative effects of peptides could potentially be utilized in fighting metabolic retinal disorders.

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“…However, no data are available in women. Based mainly on the cytoprotective functions of PACAP, there are several promising data for its potential future therapeutic use, such as in diabetes ( 117 ), multiple sclerosis ( 118 ), the intranasal administration in neurodegenerative diseases, cognitive impairment and stroke ( 119 – 121 ), in form of eye drops in corneal and retinal lesions ( 122 , 123 ) and dry eye disease ( 124 ). In contrast, the migraine-provoking effect of PACAP has drawn the interest towards antagonizing PACAP’s effects in migraine therapy ( 125 , 126 ).…”

Section: Human Findingsmentioning

confidence: 99%

Female reproductive functions of the neuropeptide PACAP

Koppán¹,

Nagy²,

Bosnyak³

et al. 2022

Front. Endocrinol.

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Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide originally isolated as a hypothalamic peptide. It has a widespread distribution in the body and has a diverse spectrum of actions. Among other processes, PACAP has been shown to be involved in reproduction. In this review we summarize findings related to the entire spectrum of female reproduction. PACAP is a regulatory factor in gonadal hormone production, influences follicular development and plays a role in fertilization and embryonic/placental development. Furthermore, PACAP is involved in hormonal changes during and after birth and affects maternal behavior. Although most data come from cell cultures and animal experiments, increasing number of evidence suggests that similar effects of PACAP can be found in humans. Among other instances, PACAP levels show changes in the serum during pregnancy and birth. PACAP is also present in the human follicular and amniotic fluids and in the milk. Levels of PACAP in follicular fluid correlate with the number of retrieved oocytes in hyperstimulated women. Human milk contains very high levels of PACAP compared to plasma levels, with colostrum showing the highest concentration, remaining steady thereafter for the first 7 months of lactation. All these data imply that PACAP has important functions in reproduction both under physiological and pathological conditions.

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

Cited by 16 publications

References 53 publications

Distribution of PACAP and PAC1 Receptor in the Human Eye

Distribution of PACAP and PAC1 Receptor in the Human Eye

Relevance of Peptide Homeostasis in Metabolic Retinal Degenerative Disorders: Curative Potential in Genetically Modified Mice

Female reproductive functions of the neuropeptide PACAP

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