Innervation of the Uvea by Galanin and Somatostatin Immunoreactive Axons in Macaques and Baboons

Abstract

The neuropeptide galanin has not been localized previously in the primate uvea, and the neuropeptide somatostatin has not been localized in the uvea of any mammal. Here, the distribution of galanin-like and somatostatin-like immunoreactive axons in the iris, ciliary body and choroid of macaques and baboons using double and triple immunofluorescence labeling techniques and confocal microscopy was reported. In the ciliary body, galanin-like immunoreactive axons innervated blood vessels and the ciliary processes, particularly at their bases. In the iris, the majority of these axons was associated with the loose connective tissue in the stroma. Somatostatin-like immunoreactive axons were found in many of the same areas of the uvea supplied by cholinergic nerves. In the ciliary body, there were labelled axons within the ciliary processes and ciliary muscle. They were also found alongside blood vessels in the ciliary stroma. In the iris, somatostatin-like immunoreactive axons were abundant in the sphincter muscle and less so in the dilator muscle. A unilateral sympathectomy had no effect on the distribution of somatostatin-like or galanin-like immunoreactive axons, and these axons did not contain the sympathetic marker tyrosine hydroxylase. They did not contain the parasympathetic marker choline acetyltransferase, either. The galanin-like immunoreactive axons contained other neuropeptides found in sensory nerves, including calcitonin gene-related peptide, substance P and cholecystokinin. Somatostatin-like immunoreactive axons did not contain any of these sensory neuropeptides or galanin-like immunoreactivity, and they were neither labelled with an antibody to 200 kDa neurofilament protein, nor did they bind isolectin-IB 4 . Nevertheless, they are likely to be of sensory origin because somatostatin-like immunoreactive perikarya have previously been localized in the trigeminal ganglion of primates. Taken together, these findings indicate galanin and somatostatin are present in two different subsets of sensory axons in primate uvea.

Antiangiogenic antitumor activities of IGFBP-3 are mediated by IGF-independent suppression of Erk1/2 activation and Egr-1–mediated transcriptional events

“…However, studies have shown that IGFBP-3 also has IGF-independent antitumor activity. 4,33 To determine whether Egr-1 transcription regulation by IGFBP-3 is IGF dependent, we cotransfected H460 cells with a human Egr-1 reporter construct and expression vectors carrying K-ras (V12) or H-ras (V12), along with pBP-3 or an empty vector control.…”

“…[4][5][6][7][8] It may also have IGF-independent antitumor activities through cell-surface or intracellular protein interaction, its nuclear translocation, or its transcriptional regulation. 7,[9][10][11][12] However, the mechanisms that mediate IGFBP-3's IGF-independent antitumor activity have not been clearly defined.…”

“…However, studies have shown that IGFBP-3 also has IGF-independent antitumor activity. 4,33 To determine whether Egr-1 transcription regulation by IGFBP-3 is IGF dependent, we cotransfected H460 cells with a human Egr-1 reporter construct and expression vectors carrying K-ras (V12) or H-ras (V12), along with pBP-3 or an empty vector control.Transfection with pBP-3 resulted in substantial loss of the Egr-1 promoter activity that had been stimulated by K-ras (V12) and H-ras (V12; Figure 4A). Egr-1 transcription is known to be activated by environmental stresses, such as hypoxia and radiation.…”

Differential Impacts of Insulin-Like Growth Factor-Binding Protein-3 (IGFBP-3) in Epithelial IGF-Induced Lung Cancer Development

“…IGF bioavailability is regulated by a family of six IGFbinding proteins (IGFBP), of which IGFBP-3 is the major IGF carrier protein in the serum (11). Previous studies have demonstrated that the serum IGF-I level in mice is significantly reduced when IGFBP-3, IGFBP-4, and IGFBP-5 are lost (12), and reduced levels of circulating IGF-I delay the onset of mammary tumor formation and suppress growth and metastasis of colon cancer (13,14).…”

Role of neuropeptides in migraine: where do they stand in the latest expert recommendations in migraine treatment?

“…SP, CGRP and CCK coexist in galanin-like immunoreactive axons (but not in SST containing fibers) in the iris, ciliary body, and choroid of macaques and baboons [Firth et al, 2002]. Electrical stimulation of the greater occipital nerve in rat had varying combinations of conjunctival injection, tearing, diminished eye aperture and miosis or mydriasis on the stimulated side of about one-third of the animals [Vincent et al, 1992].…”