Secretoneurin in the Peripheral Ocular Innervation

Troger, Josef; Doblinger, Alfred; Leierer, Johannes; Laslop, Andrea; Schmid, E. D.; Teuchner, Barbara; Opatril, Markus; Philipp, Wolfgang; Klimaschewski, Lars; Pfaller, Kristian; Göttinger, W.; Fischer‐Colbrie, Reiner

doi:10.1167/iovs.04-0425

Cited by 23 publications

(8 citation statements)

References 68 publications

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“…Most of Group C molecules were pro‐inflammatory chemokines and cytokines (Supporting Information Table S1 and Fig S1) that peaked late in the inflammatory responses (Supporting Information Fig S2). From the category of Group A genes, we selected the following as attractive candidates for inflammatory signals: (i) the neuropeptide SN because it is stored in nerve endings (Troger et al, 2005) and was previously shown to activate the chemotactic migration and transendothelial extravasation of blood cells (Helle, 2010; Taupenot et al, 2003) and (ii) two small heat shock proteins, HSPB4 and HSPB5, because some heat shock proteins (HSPs) were previously shown to act as DAMPs (Henderson & Pockley, 2010; Joly et al, 2010; Quintana & Cohen, 2005; van Wijk & Prakken, 2010).…”

Section: Resultsmentioning

confidence: 99%

Identification of the HSPB4/TLR2/NF‐κB axis in macrophage as a therapeutic target for sterile inflammation of the cornea

Choi

Lee

et al. 2012

EMBO Mol Med

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Sterile inflammation underlies many diseases of the cornea including serious chemical burns and the common dry eye syndrome. In search for therapeutic targets for corneal inflammation, we defined the kinetics of neutrophil infiltration in a model of sterile injury to the cornea and identified molecular and cellular mechanisms triggering inflammatory responses. Neutrophil infiltration occurred in two phases: a small initial phase (Phase I) that began within 15 min after injury, and a larger second phase (Phase II) that peaked at 24–48 h. Temporal analysis suggested that the neuropeptide secretoneurin initiated Phase I without involvement of resident macrophages. Phase II was initiated by the small heat shock protein HSPB4 that was released from injured keratocytes and that activated resident macrophages via the TLR2/NF-κB pathway. The Phase II inflammation was responsible for vision-threatening opacity and was markedly suppressed by different means of inhibition of the HSPB4/TLR2/NF-κB axis: in mice lacking HSPB4 or TLR2, by antibodies to HSPB4 or by TNF-α stimulated gene/protein 6 that CD44-dependently inhibits the TLR2/NF-κB pathway. Therefore, our data identified the HSPB4/TLR2/NF-κB axis in macrophages as an effective target for therapy of corneal inflammation.

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Section: Resultsmentioning

confidence: 99%

Identification of the HSPB4/TLR2/NF‐κB axis in macrophage as a therapeutic target for sterile inflammation of the cornea

Choi

Lee

et al. 2012

EMBO Mol Med

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“…Another sensory neuropeptides neurokinin A (NKA, one of the tachykinin) and secretoneurin (generated by proteolysis of chromogranins) are present in the rat and human corneas [ 25 , 26 ]. After neonatal capsaicin treatment, NKA- and secretoneurin-ir small neurons decreased by 50–60% in the rat TG [ 25 , 26 ]. In addition to the classic neurotransmitters SP and CGRP, both NKA and secretoneurin may play a role in the corneal function.…”

Section: Structure and Distribution Of Corneal Nervesmentioning

confidence: 99%

“…Although there are many peptidergic, AchE (+), or nonpeptidergic IB4 (+) nerve fibers in small neurons in the DRG and TG of mammals, it should be noted that a considerable number of capsaicin-resistant small sensory neurons always remained within them after neonatal capsaicin treatment [ 25 , 26 , 29 , 30 ].…”

Section: Structure and Distribution Of Corneal Nervesmentioning

confidence: 99%

Corneal Nerve Fiber Structure, Its Role in Corneal Function, and Its Changes in Corneal Diseases

Eguchi

Hiura

Nakagawa

et al. 2017

BioMed Research International

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Recently, in vivo confocal microscopy is used to examine the human corneal nerve fibers morphology. Corneal nerve fiber architecture and its role are studied in healthy and pathological conditions. Corneal nerves of rats were studied by nonspecific acetylcholinesterase (NsAchE) staining. NsAchE-positive subepithelial (stromal) nerve fiber has been found to be insensitive to capsaicin. Besides, NsAchE-negative but capsaicin-sensitive subbasal nerve (leash) fibers formed thick mesh-like structure showing close interconnections and exhibit both isolectin B4- and transient receptor potential vanilloid channel 1- (TRPV1-) positive. TRPV1, TRPV3, TRPA (ankyrin) 1, and TRPM (melastatin) 8 are expressed in corneal nerve fibers. Besides the corneal nerve fibers, the expressions of TRPV (1, 3, and 4), TRPC (canonical) 4, and TRPM8 are demonstrated in the corneal epithelial cell membrane. The realization of the importance of TRP channels acting as polymodal sensors of environmental stresses has identified potential drug targets for corneal disease. The pathophysiological conditions of corneal diseases are associated with disruption of normal tissue innervation, especially capsaicin-sensitive small sensory nerve fibers. The relationships between subbasal corneal nerve fiber morphology and neurotrophic keratopathy in corneal diseases are well studied. The recommended treatment for neurotrophic keratopathy is administration of preservative free eye drops.

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“…SN-containing nerve fibers are closely associated with blood vessels in the uterus [48], the nasal mucosa [46], the dental pulp [49] and in the human eye [50]. The close association with blood vessels in the uterus is of particular interest, because in this organ formation of new blood vessels (angiogenesis) occurs on a physiological basis also in the adult organism during the menstrual cycle.…”

Section: Angiogenesis and Vasculogenesismentioning

confidence: 99%

Secretoneurin: A New Player in Angiogenesis and Chemotaxis Linking Nerves, Blood Vessels and the Immune System

Fischer‐Colbrie

Kirchmair²,

Kähler³

et al. 2005

CPPS

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Secretoneurin (SN) represents a 33 amino acid neuropeptide, which is highly conserved between mammals, reptiles, birds, amphibians and fish. It is specifically expressed in endocrine, neuroendocrine and neuronal tissues. In brain, the pattern of SN expression is widespread and unique, partially overlapping with established neurotransmitters. ProSN, the precursor protein, also named secretogranin II, belongs to a class of proteins collectively called chromogranins. Changes in ProSN mRNA, which is significantly regulated by cell depolarisation, represent a useful marker for both rapid and long-lasting changes (positive and negative) of neuronal activity. Under pathophysiological conditions, especially following cellular hypoxia, SN expression can be induced in non-endocrine tissues like muscle cells, pneumocytes or tumor epithelial cells. Several biological effects were attributed to SN. SN releases dopamine from rat striatal slices in a dose dependent manner and influences neurite outgrowth in the developing cerebellum. It potently and specifically attracts monocytes, eosinophils and endothelial cells towards a concentration gradient and acts as an angiogenic cytokine comparable in potency to VEGF. Thus, SN contributes to neurogenic inflammation and might play a role in the (hypoxia-driven) induction of neo-vascularisation in ischemic diseases like peripheral or coronary artery disease, diabetic retinopathia, cerebral ischemia or in solid tumors. The signalling pathways of various biological effects have not been identified in detail, but most data point to a G-protein coupled receptor structure with respective associated intracellular events.

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Secretoneurin in the Peripheral Ocular Innervation

Cited by 23 publications

References 68 publications

Identification of the HSPB4/TLR2/NF‐κB axis in macrophage as a therapeutic target for sterile inflammation of the cornea

Identification of the HSPB4/TLR2/NF‐κB axis in macrophage as a therapeutic target for sterile inflammation of the cornea

Corneal Nerve Fiber Structure, Its Role in Corneal Function, and Its Changes in Corneal Diseases

Secretoneurin: A New Player in Angiogenesis and Chemotaxis Linking Nerves, Blood Vessels and the Immune System

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