ORCID Profile
0000-0001-7916-0397
Current Organisation
Pontifícia Universidade Católica de São Paulo
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Publisher: Elsevier BV
Date: 09-2015
DOI: 10.1016/J.EXER.2015.06.024
Abstract: The neuropeptide galanin (GAL) is widely distributed within intrinsic and extrinsic sources supplying the eye. It is involved in regulation of the vascular tone, thus important for ocular homeostasis. Since the presence/distribution of its receptors is unknown, we here screen for the presence of the various GAL receptors in the human eye. Meeting the Helsinki-Declaration, human eyes (n = 6 45-83 years of age, of both sex, post mortem time 10-19 h) were obtained from the cornea bank and prepared for immunohistochemistry against GAL receptors 1-3 (GALR1-GALR3). Over-expressing cell assays served as positive controls and confocal laser-scanning microscopy was used for documentation. Cell assays reliably detected immunoreactivity for GALR1-3 and cross-reactions between antibodies used were not observed. In the cornea, GALR1-3 were detected in basal layers of the epithelium, stroma, endothelium, as well as in adjacent conjunctiva. In the iris, GALR1-3 were detected in iris sphincter and dilator, while iris vessels displayed immunoreactivity for GALR1 and GALR3. In the ciliary body, GALR1 was exclusively found in the non-pigmented epithelium while GALR3 was detected in the ciliary muscle and vessels. In the retina, GALR1 was present in fibers of the IPL, OPL, NFL, many cells of the INL and few cells of the ONL. GALR2 and GALR3 were present in few neurons of the INL, while GALR2 was also found surrounding retinal vessels. RPE displayed weak immunoreactivity for GALR2 but intense immunoreactivity for GALR3. In the choroid, GALR1-3 were detectable in intrinsic choroidal neurons and nerve fibers of the choroidal stroma, and all three receptors were detected surrounding choroidal blood vessels, while the choriocapillaris was immunoreactive for GALR3 only. This is the first report of the various GALRs in the human eye. While the presence of GALRs in cornea and conjunctiva might be relevant for wound healing or inflammatory processes, the detection in iris vessels (GALR1, 2) and choroidal vessels (GALR1-3) highlights the role of GAL in vessel dynamics. Presence of GALR1 in ciliary body epithelium and GALR3 in ciliary vessels indicates involvement in aqueous humor production, whereas retinal GALR distribution might contribute to signal transduction.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 19-10-2015
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 14-10-2014
Publisher: Elsevier BV
Date: 2013
DOI: 10.1016/J.EXER.2012.11.009
Abstract: Alarin is a recently discovered regulatory peptide with vasoconstrictive properties in murine skin. Control of vasoconstriction/-relaxation is essential for ocular blood flow and hence the eye's homeostasis, and regulatory peptides are involved in regulation of ocular blood flow. Here we describe the existence and distribution of alarin in the eye of human and potential experimental animals (rat, mouse). Eyes of rat, mouse, and human were prepared for immunohistochemistry against murine and human alarin, respectively. Additionally, double staining experiments for alarin and CD31 were performed in human choroidal flat-mount preparations. For documentation, confocal laser scanning microscopy was used while quantitative real-time-PCR was applied to confirm immunohistochemical data and to detect alarin mRNA expression in human retina and choroid. Alarin-like immunoreactivity (alarin-LI) was detected in corneal epi- and endothelium of human, mouse, and rat, as well as in the conjunctiva of mouse and rat. Alarin-LI was found in the iris of all the species investigated and, in humans, was concentrated around blood vessels. All three species showed distinctive alarin-LI in the non-pigmented epithelium of the ciliary body. In the retina of mouse and rat, maximum signals were detected in the outer nuclear and ganglion cell layer, whereas in humans a strong alarin-LI was found around retinal blood vessels and in intrinsic choroidal neurons (ICN). Quantitative RT-PCR in human confirmed alarin mRNA expression retina and choroid. The existence of alarin in cornea and conjunctiva might indicate a role in immune defense, while its presence in the non-pigmented ciliary epithelium favors an involvement in aqueous humor production. Alarin around blood vessels/in ICN might indicate an involvement in ocular blood flow regulation. Since alarin is found widely distributed in the eyes of species investigated, we were able to establish the basis for further functional experiments.
Publisher: Elsevier BV
Date: 08-2017
DOI: 10.1016/J.NPEP.2016.11.007
Abstract: Galanin (GAL) is a neuro-regulatory peptide involved in many physiological and pathophysiological processes. While data of GAL origin/distribution in the human eye are rather fragmentary and since recently the presence of GAL-receptors in the normal human eye has been reported, we here systematically search for sources of ocular GAL in the human eye. Human eyes (n=14) were prepared for single- and double-immunohistochemistry of GAL and neurofilaments (NF). Cross- and flat-mount sections were achieved confocal laser-scanning microscopy was used for documentation. In the anterior eye, GAL-immunoreactivity (GAL-IR) was detected in basal layers of corneal epithelium, endothelium, and in nerve fibers and keratinocytes of the corneal stroma. In the conjunctiva, GAL-IR was seen throughout all epithelial cell layers. In the iris, sphincter and dilator muscle and endothelium of iris vessels displayed GAL-IR. It was also detected in stromal cells containing melanin granules, while these were absent in others. In the ciliary body, ciliary muscle and pigmented as well as non-pigmented ciliary epithelium displayed GAL-IR. In the retina, GAL-IR was detected in cells associated with the ganglion cell layer, and in endothelial cells of retinal blood vessels. In the choroid, nerve fibers of the choroidal stroma as well as fibers forming boutons and surrounding choroidal blood vessels displayed GAL-IR. Further, the majority of intrinsic choroidal neurons were GAL-positive, as revealed by co-localization-experiments with NF, while a minority displayed NF- or GAL-IR only. GAL-IR was also detected in choroidal melanocytes, as identified by the presence of intracellular melanin-granules, as well as in cells lacking melanin-granules, most likely representing macrophages. GAL-IR was detected in numerous cells and tissues throughout the anterior and posterior eye and might therefore be an important regulatory peptide for many aspects of ocular control. Upcoming studies in diseased tissue will help to clarify the role of GAL in ocular homeostasis.
Publisher: Elsevier BV
Date: 02-2015
DOI: 10.1016/J.EXER.2014.12.007
Abstract: Extrinsic and intrinsic sources of the autonomic nervous system contribute to choroidal innervation, thus being responsible for the control of choroidal blood flow, aqueous humor production or intraocular pressure. Neuropeptides are involved in this autonomic control, and amongst those, alarin has been recently introduced. While alarin is present in intrinsic choroidal neurons, it is not clear if these are the only source of neuronal alarin in the choroid. Therefore, we here screened for the presence of alarin in human cranial autonomic ganglia, and also in rat, a species lacking intrinsic choroidal innervation. Cranial autonomic ganglia (i.e., ciliary, CIL pterygopalatine, PPG superior cervical, SCG trigeminal ganglion, TRI) of human and rat were prepared for immunohistochemistry against murine and human alarin, respectively. Additionally, double staining experiments for alarin and choline acetyltransferase (ChAT), tyrosine hydroxilase (TH), substance P (SP) were performed in human and rat ganglia for unequivocal identification of ganglia. For documentation, confocal laser scanning microscopy was used, while quantitative RT-PCR was applied to confirm immunohistochemical data and to detect alarin mRNA expression. In humans, alarin-like immunoreactivity (alarin-LI) was detected in intrinsic neurons and nerve fibers of the choroidal stroma, but was lacking in CIL, PPG, SCG and TRI. In rat, alarin-LI was detected in only a minority of cranial autonomic ganglia (CIL: 3.5% PPG: 0.4% SCG: 1.9% TRI: 1%). qRT-PCR confirmed the low expression level of alarin mRNA in rat ganglia. Since alarin-LI was absent in human cranial autonomic ganglia, and only present in few neurons of rat cranial autonomic ganglia, we consider it of low impact in extrinsic ocular innervation in those species. Nevertheless, it seems important for intrinsic choroidal innervation in humans, where it could serve as intrinsic choroidal marker.
Publisher: Springer Science and Business Media LLC
Date: 05-01-2019
DOI: 10.1007/S00418-018-1763-9
Abstract: Alarin (AL), a new member of the galanin family, has been localized in various CNS regions, mainly in rodents. Among other effects, it modulates food intake. Therefore, we analyzed the immunohistochemical distribution pattern of AL in human intestinal epithelia. Cryosections of 12 human bowel s les were immunohistochemically double-stained for AL and α-defensin 5 (αD first set). Two further sets of sections were quadruple-stained either (second set) for AL, chromogranin (CG), synaptophysin (SY), and somatostatin (SO) or (third set) for AL, CG, Peptide Y (PY), and 5-hydroxytryptamine (5-HT). Slides were digitized and quantitative analysis of co-localization rates was undertaken. Small bowel: most of AL-positive cells (56%) were αD-positive Paneth cells located within the base of the crypts (first set). In the second set, about 27% of AL-labeled cells were co-reactive for SY and CG, likely representing entero-endocrine cells. In the third set, the largest subpopulation of AL-positive cells was not co-reactive for other markers applied (89%) most of them were likely Paneth cells. Large bowel: co-localization of AL with αD was not detected (first set). In the second set, AL was frequently co-localized with the other three markers applied (68%). In the third set, AL was frequently co-localized with 5-HT and CG (31%) as well as with PY and 5-HT (22%). Due to its presence in various enteroendocrine as well as Paneth cells, AL may be involved in different physiological and pathological processes.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Start Date: 2017
End Date: 2019
Funder: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
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