The role of the pro-ghrelin derived peptides in the iris muscle regulation: Implications in glaucoma pathophysiology

• Type: Chapter or Part of a Book
• Date: 2012

Authors

Azevedo Pinto, S (Author) Other; Tavares Silva, M (Author) FMUP; Pereira Silva, P (Author) Other; Leite-Moreira AF (Author) FMUP; Rocha-Sousa A (Author) FMUP

Book

Title: Ghrelin: Production, Action Mechanisms and Physiological Effects

Pages: 33-56

ISBN: 9781619424005

Indexing

Scopus - 0 Citations

Other information

Authenticus ID: P-00G-MRH

Abstract (EN): Ghrelin is a 28 aminoacid peptide first described in the rat's stomach oxyntic musosa in 1999 by Kojima et al. This peptide derives from the pro-ghrelin and is the endogenous ligand of the growth hormone secretagogues receptor-type 1a (GHSR-1a), being ghrelin's acylation in the serine 3 residue essential for this linkage. There is also a non acylated ghrelin form, des-octanoil-ghrelin, which does not bind GHSR-1a and represents 90% of the circulating hormone. Ghrelin exerts its actions through different subcellular pathways, being the GHSR-1a related to the IP3-DAG pathway. Besides promoting growth hormone release from the pituitary, ghrelin exerts its actions in several organ systems, namely the endocrine, cardiovascular, musculo-skeletal and the eye, among others. Nowadays, it is accepted that there are other receptors responsible for ghrelin's action than GHSR-1a. Through an alternative splicing method, pro-ghrelin may also originate another peptide, called obestatin. Obestatin, a 23 aminoacid peptide, was first isolated through bioinformatic techniques, being subsequently described in both rat's and human stomach. This peptide has been reported to exert actions opposite to those of ghrelin in several systems, such as the endocrine system. All these pro-ghrelin derived peptides have been proven to exert significant effects in the several components of the ocular tissue. The ghrelin-obestatin system has recently been described to exert an active role on the kinetics of the iris sphincter muscle. On the one hand, ghrelin promotes the decrease of the muscle's tension, either the actively developed after carbachol pre-contraction, or the basal one. This relaxing effect is not species dependent, being independent from GHSR-1a and from nitric oxide and dependent on prostaglandins' production. On the other hand, obestatin showed to potentiate the iris' sphincter muscle cholinergic contraction, although when the muscle stimulation was achieved through electrical field stimulation it seemed to induce a tendency of the developed tension to decrease. The other ocular muscle studied was the iris dilator muscle, a smooth muscle also presenting several pathways of neurohumoral regulation. In this muscle, ghrelin was reported to decrease the norepinephrine induced muscular contraction, through a mechanism dependent on GHSR-1a. Concerning obestatin, it decreased the iris' dilator muscle basal tension, but showed no effect on the epinephrine induced active tension. The anterior segment of the eye is also influenced by the pro-ghrelin derived peptides. Ghrelin's mRNA has been observed in the iris posterior segment and in the non pigmented cilliary epithelium. The interaction between this system and the anterior segment has also been reported in glaucoma, an optic nerve damage which presents as the main cause an increase in intra-ocular pressure. Both open angle and pseudoexfoliation glaucoma were associated with increased aqueous humor ghrelin levels, which may imply these peptides in the patophisiology of the disease. Concerning other effects in the eye, obestatin was shown to promote the proliferation of the retinal pigmented epithelium cells, through a pathway dependent on the activation of ERK 1/2, while ghrelin was implicated in the retina neovascular process.

Language: English

Type (Professor's evaluation): Scientific