Cellular terrain surrounding sympathetic nerve pathways in the rat orbit: Comparisons of orbital connective tissue and smooth muscle cell phenotypes

Abstract

Sympathetic axons are abundant within some orbital tissues but are absent from others. This study investigated cellular phenotypes of tissues containing sympathetic nerves en passage and compared these with phenotypes in regions devoid of sympathetic nerves and with smooth muscle targets. Two primary orbital smooth muscle targets, the tarsal muscle and orbital muscle, contained many synaptophysin-immunoreactive nerves. Target cells had ultrastructural features typical of smooth muscle and were immunoreactive for alpha-smooth muscle actin, smooth muscle myosin heavy chain, desmin, vinculin, and laminin, but not non-muscle myosin, vimentin, fibronectin, or type IV collagen; nerve growth factor (NGF) mRNA was detected by reverse transcription-polymerase chain reaction. Periorbital sheath devoid of sympathetic nerves contained elongated fibroblasts that were immunoreactive for vimentin, non-muscle myosin, and fibronectin, but not for alpha-smooth muscle actin, smooth muscle myosin heavy chain, vinculin, desmin, laminin, or type IV collagen, and did not express NGF mRNA. Regions of periorbital sheath containing sympathetic nerves had few synaptophysin-immunoreactive varicosities. Cells in this region contained myofilaments, ribosomes, and rough endoplasmic reticulum and were larger than tarsal muscle cells. They expressed NGF mRNA and showed a unique immunophenotype, reacting for vimentin, alpha-smooth muscle actin and myosin heavy chain, desmin, vinculin, laminin, and type IV collagen. This phenotype reflects both fibroblast and smooth muscle features similar to myofibroblasts or transdifferentiated smooth muscle described in other tissues. The spatial association between these cells and sympathetic nerves suggests that they may be involved in axon guidance or maintenance.

Relationships between nerves and myofibroblasts during cutaneous wound healing in the developing rat

“…Together, the spatial and temporal associations observed suggest that myofibroblasts may possess neurotrophic properties. In some normal tissues, nerves are frequently associated with myofibroblast-like cells (Nistal et al 1982;Saito 1990;Tamm et al 1995;Smith et al 1998), leading us to propose a neurotrophic role for these cells. Wound myofibroblasts may also regulate innervation, as they can produce extracellular matrix factors such as laminin that are known to promote neurite outgrowth (Eddy et al 1988;Berndt et al 1994), and may synthesize nerve growth factor ( Matsuda et al 1998;Hasan et al 1998), thus contributing to the high levels of this neurotrophin at the wound site (Constantinou et al 1994).…”

“…Myofibroblasts appear with the formation of granulation tissue in the early phase of wound closure, and disappear in the later stages, presumably as a result of apoptosis (Desmouliere et al 1997). While associations between wound myofibroblasts and regenerating nerves apparently have not been investigated, cells with myofibroblast features are present in some normal tissues, where they are frequently associated with nerves (Nistal et al 1982;Tamm et al 1995;Smith et al 1998).…”

Glucagon-Like Peptide-1 Mediates the Protective Effect of the Dipeptidyl Peptidase IV Inhibitor on Renal Fibrosis via Reducing the Phenotypic Conversion of Renal Microvascular Cells in Monocrotaline-Treated Rats

“…Among them, 50% arise from local resident fibroblasts via proliferation, 35% are derived via differentiation from bone marrow, 10% result from endothelial-to-mesenchymal transition (EndMT), and 5% originate from epithelial-to-mesenchymal transition (EMT) [ 6 ]. Apart from those above, cells of the synthetic phenotype of SMCs, which are derived from the contractile SMC phenotype, can reflect both fibroblast and smooth muscle features, similar to myofibroblasts [ 7 ] and also participate in renal progressive vascular sclerosis and fibrosis [ 8 , 9 ] by producing excessive matrix elements.…”

Increased Fibronectin Expression in Sturge-Weber Syndrome Fibroblasts and Brain Tissue

“…Furthermore, fibronectin has been shown to have potent effects on sympathetic nerve outgrowth and vessel innervation (26,27). Cunha e Sa et al (28) demonstrated that malformed cortical vessels in SWS are innervated only by noradrenergic sympathetic nerve fibers.…”