Microscopic Study of Nervous System Plasticity: Interactions of Sympathetic Nerves with Neurons of Intraocular Hippocampal Transplants.

Functional interactions of sympathetic fibers innervating the iris with the neurons of central origin in intraocular transplants of the rat hippocampus were studied by optic, confocal, and electron microscopy. After formaldehyde fixation, fluorescent dye Dil was applied to the upper cervical ganglion; the dye migrated to the transplant by lateral diffusion via axons. Sympathetic nerves labeled with fluorescent dye grew into the neurotransplants along perivascular membranes of blood vessels. In addition, some fluorescent axons were identified in the transplant parenchyma. Electron microscopy showed large bundles of the peripheral type axons in the vascular adventitia and Schwann-axonal complexes in the transplant neuropil. Autonomic axons formed synaptic contacts with transplanted neurons.

[Acute Sensory Neuropathies and Acute Autonomic Neuropathies].

From the perspective of neuropathies with an acute onset mimicking that of Guillain-Barré syndrome (GBS), cases with profound sensory and/or autonomic impairment without any significant weakness have been reported. Although the possibility of infectious or toxic etiologies should be carefully excluded, immune mechanisms similar to those in GBS are suggested to be involved in these so-called acute sensory neuropathies and acute autonomic neuropathies. The types of neuropathy include those with predominant sensory manifestations, predominant autonomic manifestations such as autoimmune autonomic ganglionopathy, and both sensory and autonomic manifestations such as acute autonomic and sensory neuropathy. Neuronopathy in the sensory and/or autonomic ganglia (i.e., ganglionopathy) has been commonly suggested in patients with these types of neuropathies. The presence of Anti-GD1b antibodies has been reported in some of the patients with acute sensory neuropathy with deep sensory impairment, whereas anti-ganglionic acetylcholine receptor antibodies are reported to be present in half of the patients with autoimmune autonomic ganglionopathy. The discovery of anti-ganglionic acetylcholine receptor antibodies significantly expanded the spectrum of autoimmune autonomic ganglionopathy. This is because some of the patients with chronic progression mimicking neurodegenerative diseases such as pure autonomic failure were positive for these antibodies. In contrast, pathologically significant autoantibodies have not been identified in acute autonomic and sensory neuropathy. Further studies are needed to clarify the pathogenesis and the spectrum of these types of neuropathies.

Effects of ozone and fine particulate matter (PM(2.5)) on rat system inflammation and cardiac function.

In order to understand the toxic mechanisms of cardiovascular system injuries induced by ambient PM(2.5) and/or ozone, a subacute toxicological animal experiment was designed with exposure twice a week for 3 continuous weeks. Wistar rats were randomly categorized into 8 groups (n=6): 1 control group, 3 groups exposed to fine particulate matters (PM(2.5)) alone at 3 doses (0.2, 0.8, or 3.2 mg/rat), 1 group to ozone (0.81 ppm) alone and 3 groups to ozone plus PM(2.5) at 3 doses (0.2, 0.8, or 3.2 mg/rat). Heart rate (HR) and electrocardiogram (ECG) was monitored at approximately 24-h both after the 3rd exposure and the last (6th) exposure, and systolic blood pressure (SBP) was monitored at approximately 24-h after the 6th exposure. Biomarkers of systemic inflammation and injuries (CRP, IL-6, LDH, CK), heart oxidative stress (MDA, SOD) and endothelial function (ET-1, VEGF) were analyzed after the 6th exposure. Additionally, myocardial ultrastructural alterations were observed under transmission electron microscopy (TEM) for histopathological analyses. Results showed that PM(2.5) alone exposure could trigger the significant increase of CRP, MDA, CK, ET-1 and SBP and decrease of heart rate variability (HRV), a marker of cardiac autonomic nervous system (ANS) function. Ozone alone exposure in rats did not show significant alterations in any indicators. Ozone plus PM(2.5) exposure, however, induced CRP, IL-6, CK, LDH and MDA increase, SOD and HRV decrease significantly in a dose-response way. Meanwhile, abnormal ECG types were monitored in rats exposed to PM(2.5) with and without ozone and obvious myocardial ultrastructural changes were observed by TEM. In conclusion, PM(2.5) alone exposure could cause inflammation, endothelial function and ANS injuries, and ozone potentiated these effects induced by PM(2.5).

Ultrastructural transneuronal degeneration study of axonal elements within the paratrigeminal nucleus in sinoaortic deafferented rats.

OBJECTIVE: Morphological study that searched to authenticate the presence of sinoaortic baroreceptor inputs within the dorsolateral medullary nucleus under electron microscopy analysis. METHODS: After a 5-day survival period, 9 baroreceptor-denervated rats deeply anaesthetized with equithesin were transcardially perfused and their brains were histologically processed. RESULTS: The neuronal cytoarchitecture of the paratrigeminal nucleus comprehends afferent projections from other nuclei that have a distributive character regarding visceral and nociceptive functions in the cardiovascular reflex integration response. CONCLUSION: The medial portion of the nucleus receives afferent projections of the rostral ventrolateral medulla, as shown by retrograde neurotracing studies. The present results show that the medial extent of the paratrigeminal nucleus contains degenerated axoplasmic cellular components in sinoaortic deafferented rats. The number of degenerated axonal fibers was also larger in this area of the nucleus.

Human primordial germ cells migrate along nerve fibers and Schwann cells from the dorsal hind gut mesentery to the gonadal ridge.

The aim of this study was to investigate the spatiotemporal development of autonomic nerve fibers and primordial germ cells (PGCs) along their migratory route from the dorsal mesentery to the gonadal ridges in human embryos using immunohistochemical markers and electron microscopy. Autonomic nerve fibers in the dorsal mesentery, the pre-aortic and para-aortic plexuses and in the gonadal ridge were stained for beta III tubulin, neuron specific enolase and the glia fibrillary acidic protein. Electron microscopy demonstrated the presence of neurofilaments and neurotubules in these nerve fibers and their intimate contact with PGCs. PGCs expressed GAGE, MAGE-A4, OCT4 and c-Kit. Serial paraffin sections showed that most PGCs were located inside bundles of autonomic nerve fibers with the majority adjacent to the most peripheral fibers (close to Schwann cells). We also show that both nerve fibers and PGCs arrive at the gonadal ridge between 29 and 33 days pc. In conclusion, our data suggest that PGCs in human embryos preferentially migrate along autonomic nerve fibers from the dorsal mesentery to the developing gonad where they are delivered via a fine nerve plexus.

The heat shock response modulates transthyretin deposition in the peripheral and autonomic nervous systems.

Familial amyloidotic polyneuropathy (FAP) is a neurodegenerative disease that selectively affects the peripheral nervous system. The putative cause of this life threatening pathology is tissue deposition of mutant transthyretin (TTR), initially as non-fibrillar deposits and later as fibrillar material. The mouse models currently available do not recapitulate the human whole features, since the peripheral nervous tissue is spared. We have characterized a new mouse model expressing the human transthyretin V30M in a heat shock transcription factor 1 (Hsf1) null background. The lack of HSF1 expression leads to an extensive and earlier non-fibrillar TTR, evolving into fibrillar material in distinct organs including the peripheral nervous system. Furthermore, inflammatory stress and a reduction in unmyelinated nerve fibers were observed, as in human patients. These results indicate that HSF1 regulated genes are involved in FAP, modulating TTR tissue deposition. The novel mouse model is of the utmost importance in testing new therapeutic strategies and in addressing the influence of the stress response in misfolding diseases.

The role of the autonomic nervous system in the etiology of idiopathic scoliosis: prospective electron microscopic and morphometric study.

OBJECTS: The exact etiology of scoliosis is still unknown. The main purpose of this study is to search for the possible causation of scoliosis in the development changes of autonomic nervous structures. In this prospective study, we followed-up the changes in peripheral nerve structures and its discrepancies regarding the concavity and convexity of the scoliotic curve. MATERIALS AND METHODS: We evaluated 12 patients with the idiopathic scoliotic deformity and the control group of 3 patients without any scoliotic deformity. The samples from the peripheral nerves of the convexity and concavity of the scoliotic deformity were drawn during the surgical correction by using the transthoracic approach. The samples were examined by the electron microscopic method and morphometric statistical evaluation. RESULTS: In samples taken from the scoliotic convexity, 23.71% of myelinized nerve fibers (MNF), 12.21% of unmyelinized nerve fibers (UNF), and 5.0% of Schwann cells (SC) were found by the morphometric measurement. There were 17.36% of MNF, 5.82% of UNF, and 5.27% of SC in samples taken from the concavity and 29.9% of MNF, 19.9% of UNF, and 16.7% of SC in the control nonscoliotic samples. Statistically significant differences between both sides of scoliotic deformity (convexity and concavity) and differences between the scoliotic samples and the nonscoliotic control samples were found. In all scoliotic samples, significant morphologic changes were found, mostly in the myelin sheaths and axon fiber abnormalities compression. CONCLUSION: There are significant morphologic changes in spinal autonomic nervous structures in scoliotic patients. These findings can help us in the search for the etiology of scoliosis.

Alterations in the ultrastructure of cardiac autonomic nervous system triggered by crotoxin from rattlesnake (Crotalus durissus cumanensis) venom.

This study explored the toxic effects of crotoxin isolated from Crotalus durissus cumanensis venom on the ultrastructure of mice cardiac autonomic nervous system. Mice were intravenously injected with saline (control group) and crotoxin diluted in saline venom (study group) at a dose of 0.107 mg/kg mouse body weight. Samples from the inter-ventricular septum were prepared for electron microscopy after 6 h (G1), 12 h (G2), 24 h (G3) and 48 h (G4). The G1 group showed some cardiomyocyte with pleomorphic mitochondria. Capillary swollen walls, nerve cholinergic endings with depleted acetylcholine vesicles in their interior and other depletions were observed. A space completely lacking in contractile elements was noticed. The G2 group demonstrated a myelinic figure, a subsarcolemic region with few myofibrils and nervous cholinergic terminal with scarce vacuoles in their interior. The G3 group demonstrated a structure with a depleted axonic terminal, mitochondrias varying in size and enhanced electron density. In addition, muscular fibers with myofibrillar structure disorganization, a depleted nervous structure surrounded by a Schwann cell along with an abundance of natriuretic peptides, were seen. An amyelinic terminal with depleted Schwann cell and with scarce vesicles was also observed. Finally, axonic lysis with autophagic vacuoles in their interior and condensed mitochondria was observed in the G4 group. This work describes the first report of ultrastructural damage caused by crotoxin on mice cardiac autonomic nervous system.

Hypothalamic projections to locus coeruleus neurons in rat brain.

Locus coeruleus (LC) neurons respond to autonomic and visceral stimuli and discharge in parallel with peripheral sympathetic nerves. The present study characterized the synaptic organization of hypothalamic afferents with catecholaminergic neurons in the LC using electron microscopy. Peroxidase labeling of axon terminals that were anterogradely labeled from the paraventricular nucleus (PVN) was combined with gold-silver labeling of tyrosine hydroxylase in the LC. Approximately 19% of the anterogradely labeled axon terminals formed synaptic specializations with tyrosine hydroxylase-immunoreactive dendrites in the LC. Retrograde transport from the LC combined with immunocytochemical detection of enkephalin and corticotropin-releasing factor (CRF) suggested that most of the LC-projecting PVN neurons (30%) were CRF immunoreactive and few (2%) were enkephalin immunoreactive. Finally, dual retrograde tracing from the LC and median eminence revealed that PVN neurons that project to the LC are a population distinct from that projecting to the median eminence. The present data suggest that a population of hypothalamic neurons is poised to directly modulate the activity of LC neurons and may integrate autonomic responses in brain by influencing LC neurons. Moreover, PVN neurons that use CRF as a neurohormone are distinct from those that use CRF as a neuromodulator to impact on the LC.

Ultrastructural studies of gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the gastrointestinal tract (GIT). Although interstitial cells of Cajal has been suggested as origin of this tumor, the cytological and ultrastructural features of GISTs are heterogeneous and unclear. A total 10 cases of normal gastrointestinal tissue (control), 13 GISTs of the stomach (8), small intestine (3), mesocolon (1) and liver (1), and 2 gastrointestinal autonomic nervous tumor (GANT) of small intestine were ultrastructurally studied. Normal interstitial cells of Cajal (ICC) were abundantly present around the myenteric plexuses or individually scattered through the wall of GIT. ICC was characterized by slender cytoplasmic processes, well-developed endoplasmic reticulum (ER), mitochondria, Golgi apparatus, caveolae and intermediate filaments. The GISTs and GANTs had overlapping ultrastructures. The most common and important ultrastructural features of GISTs were rich villous cytoplasmic processes, dispersed intermediate filaments and abundant SER, and those of GANTs were neurosecretory granules and skenoid fibers. Compared with ICC, the GISTs and GANTs had remarkably reduced caveolae and gap junctions. Our study suggested that ultrastructural analysis gives much information to investigate lineage differentiation of neoplastic cells and make a differential diagnosis of these tumors from other mesenchymal tumors and between GISTs and GANTs.

Familial amyloid polyneuropathy: mechanisms leading to nerve degeneration.

Familial amyloid polyneuropathy (FAP) manifests itself as a fiber-length-dependent polyneuropathy predominantly affecting sensory and autonomic nervous systems. Endoneurial amyloid deposits can be noxious to nerve fibers in several ways including mechanical and toxic effects on nerve fibers, and impairment of blood supply. On teased fiber preparations, a mixture of axonal degeneration and a lower proportion of segmental demyelination is observed. Within a few years of the first symptoms there is a near complete disappearance of myelinated and unmyelinated nerve fibers in the nerve samples taken by biopsy. On teased fiber preparations, amyloid deposits induce distortion, demyelination and eventually distal axonal degeneration of neighboring nerve fibers. This "mechanical" effect is associated with a "toxic" effect of amyloid fibrils leading to the disappearance of the basal lamina of Schwann cells, followed by death, presumably by apoptosis. Amyloid deposits often cluster around endoneurial blood vessels, and even invade their wall with subsequent occlusion of endoneurial vessels themselves.

Axons in human choroidal melanoma suggest the participation of nerves in the control of these tumors.

PURPOSE: To furnish morphologic evidence of autonomic nervous system influence on choroidal melanoma. DESIGN: Histopatholgic case report. METHODS: In the enucleated eye of a 72-year-old woman, portions of a mixed-cell choroidal melanoma were processed for electron microscopy, and ultrathin sections were screened painstakingly under magnifications of x13,000 and x23,000. RESULTS: The connective tissue of the melanoma contained macrophages, blood vessels, and profiles of several nonmyelinated nerve fiber bundles with a maximum of 6 axons. CONCLUSION: The existence of axons in neoplastic tissue indicates nervous input and/or output. This led us to conclude that the reaction of the melanoma is subjected to vegetative influences, yet to an unknown extent.

Alpha(2A)-adrenergic receptors are present in mu-opioid receptor containing neurons in rat medial nucleus tractus solitarius.

Agonists of the alpha-2A-adrenergic- (alpha(2A)-AR) and the mu-opioid-receptor (muOR) jointly affect autonomic functions that are also disregulated in animals undergoing withdrawal from chronic administration of the muOR agonist morphine. Cardiovascular and gastrointestinal reflexes are mediated, in part, by the medial nucleus of the solitary tract (mNTS) at caudal (cNTS) and intermediate (iNTS) subregions. Together, this evidence suggests that alpha(2A)-AR and muOR may be colocalized within many of the same neuronal profiles in both the intermediate and caudal mNTS. In order to examine whether alpha(2A)-AR and muOR are present within common somata, dendrites, or axon terminals in the mNTS, we used electron microscopic immunocytochemistry for the detection of antisera against each receptor at intermediate and caudal levels of this brain region. Most of the dually labeled profiles were somata and dendrites. Of all dual-labeled profiles in the iNTS 49% were somata and were 47% dendrites, whereas in the cNTS 61% were somata and 32% were dendrites. Within dual-labeled profiles, the intracellular distribution of alpha(2A)-AR and muOR differed. MuOR was more frequently associated with the plasmalemma, whereas alpha(2A)-AR was often affiliated with vesicular organelles. Few axon terminals, and even fewer glia, contained both markers. We also frequently observed single-labeled alpha(2A)-AR glia that apposed exclusively muOR-containing dendrites or axon terminals. These findings indicate that somata and dendrites contain functional sites for convergent muOR and alpha(2A)-AR activation. In addition, each receptor is positioned for involvement in intercellular signaling between apposed neurons and glia. Activation of alpha(2A)-AR on muOR-containing somata or dendrites, or on glia apposed to muOR-containing neurons, may help to account for the efficacy of alpha(2A)-AR agonists in relieving some of the autonomic symptoms of opiate withdrawal.

Immunohistochemical and electron microscopic study of extrinsic hepatic reinnervation following orthotopic liver transplantation in rats.

BACKGROUND/AIMS: Because little has been known about the morphological and functional consequences of liver transplantation on hepatic autonomic nerves, we examined the time-course of extrinsic hepatic innervation at the level of the porta hepatis of liver allografts. METHODS: Orthotopic liver transplantation was performed using male Lewis rats. Crosscut tissue specimens were obtained postoperatively for up to 6 months from the porta hepatis of transplanted livers, and processed for immunohistochemical staining for protein gene product 9.5 (PGP 9.5) and growth-associated protein 43 (GAP-43), and for transmission electron microscopy (TEM). RESULTS: Extrinsic nerve fibers at the porta hepatis stained positively for PGP 9.5 throughout the entire study period. In contrast, the immunoreactivity of GAP-43 was negative at postoperative day (POD) 1 and 2. GAP-43-positive nerves were first observed to appear in the porta hepatis at POD 3. The immunoreactivity of GAP-43 remained positive thereafter until 3 months post-OLT, and became negative in all the specimens at 4 months post-OLT. Transmission electron microscopy demonstrated a small number of regenerating axons existing among many degenerating axons at POD 3. At 3 months post-OLT, most regenerating axons had been fully ensheathed by the cytoplasm of Schwann cells, although their density remained at a lower level compared with normal. CONCLUSION: The results of this study suggest that liver allografts become extrinsically reinnervated, with the regenerating axons reaching the hepatic hilus 3 days after transplantation. The process of extrinsic hepatic reinnervation is considered to almost terminate 4 months after transplantation in rats.

Ultrastructural deficiency in autonomic innervation in cremasteric muscle of boys with undescended testis.

BACKGROUND/PURPOSE: The cremaster muscles (CM) associated with undescended testis reveal neurogenic alterations that mainly affect type 2 fibers. The ultrastructure of CM has been evaluated to define if further evidence to explain the alterations could be identified. METHODS: CM of 8 boys with inguinal hernia and 8 boys with undescended testis at similar ages were biopsied. Samples were processed for electron microscopic evaluations. Semithin and thin sections were examined under an electron microscope. RESULTS: The CM associated with inguinal hernia showed normal ultrastructure. However, some alterations were encountered in CM associated with undescended testis. Unmyelinated fibers were diminished in number, and myelinated fibers were outnumbering the unmyelinated fibers. Marked disorientation of myofibers, redundant sarcolemma, empty sleeves of basal lamina, disarray of myofibrils, densely packed myofilaments, Z disk streaming, dilated sarcoplasmic reticulum, and dense-irregularly shaped mitochondria were repeatedly encountered. Satellite cells appeared inactive. Most of the fibers were contracted. CONCLUSIONS: The decrease in number of unmyelinated fibers appears to represent a decrease in autonomic nerve fibers. The alterations within muscle fibers may reflect a deficiency in autonomic innervation. Autonomic nervous system is highly responsive to circulating androgens. Factors decreasing the vulnerability of autonomic nervous system against androgenic effects may result in a CM with neurogenic alterations, thus inhibiting testicular descent. J Pediatr Surg 36:573-578.

Immunolocalization of the HNK-1 epitope in the autonomic innervation to the liver and upper digestive tract of the developing rat embryo.

The immunohistochemical analysis of the HNK-1 epitope presence in the liver and upper digestive tract nerves was carried out in 12- to 18-day-old rat embryos embedded in acrylamide-agarose and observed with laser scanning confocal microscopy. The vagus and sympathetic trunk were intensely immunostained at all ages; branches of both structures were also HNK-1 positive, and ramified ventrocaudally following the course of the thoracic and abdominal aorta, caval vein, portal vein and ductus venosus. As early as day 12, some immunostained cells were seen in the mesentery that formed the enteric nervous system. Clearly immunostained HNK-1-immunoreactive fibres were detected innervating the digestive wall after day 14, forming both myenteric and submucosal plexuses. After day 16, the Glisson sheath showed streams of HNK-1-positive fibres coming from dorsal areas, lining the peritoneal surface of the diaphragm, invading the capsule, and ramifying superficially around the lobes of the liver. We saw no immunoreactive structures pervading the hepatic lobes at all ages studied, with the exception of occasional HNK-l-positive cells in the superficial parenchyma, which were visualized after 16 days of gestation. Our findings can help to understand the development of the gastrointestinal and liver innervation in the rat.

Autonomic nervous system and smooth muscle cell involvement in systemic sclerosis: ultrastructural study of 3 cases.

OBJECTIVE: To investigate morphological abnormalities in nerve and smooth muscle structures of the anorectal wall underlying gastrointestinal dysfunction in patients with systemic sclerosis (SSc). METHODS: We performed deep rectal biopsy in 3 patients with limited scleroderma of relatively recent onset and intestinal symptoms. RESULTS: We found ultrastructural signs of axonal degeneration and cytoskeletal abnormalities in the bundles of unmyelinated fibers. There was also focal degeneration of smooth muscle cells, often in association with the presence of partially degranulated mast cells. Many mast cells were also observed in close relation to nerve fibers and vessels. The enteric vessels often showed basal lamina reduplication and hypertrophied endothelial cells with obliterated lumen. No significant fibrosis was found. CONCLUSION: Our findings indicate early involvement of the autonomic nervous system and to a lesser extent of smooth muscle cells. We confirmed the presence of early vascular lesions and involvement of mast cells in the pathological process.

Autonomic nerves containing substance P in the aqueous outflow channels and scleral spur of the guinea pig.

PURPOSE: To study the innervation of the aqueous outflow channels and scleral spur by autonomic nerves containing substance P. METHODS: The experiments were conducted on guinea pigs. Immunohistochemical techniques and capsaicin-ablation of the sensory nerves were used to investigate nerves containing substance P at the light and electron microscopic level. RESULTS: Nerves containing substance P were observed in the aqueous outflow channels and scleral spur regions. The fine structures of these nerves had a similar pattern in those regions, and the labeled elements had abundant small vesicles, a few large vesicles, and numerous neurotubuli. Following capsaicin treatment, these nerves remained intact and no degenerated substance P-like immunoreactive nerves were found. CONCLUSIONS: Nerves containing substance P are most likely of autonomic origin in view of their ultrastructural features. These nerves innervate the aqueous outflow channels and scleral spur, and are probably important for neurogenic influences on the intraocular pressure by the autonomic nervous system.

Differential expression of group I metabotropic glutamate receptors in rat spinal cord somatic and autonomic motoneurons: possible implications for the pathogenesis of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the progressive loss of somatic, but not autonomic, motoneurons. The reason for this selective vulnerability is unknown. The pathogenesis of ALS is thought to involve glutamatergic excitotoxic mechanisms. While overactivation of ionotropic glutamate receptors may trigger excitotoxicity, we have previously shown that stimulation of group I metabotropic glutamate receptors (mGluRs) can exert neuroprotective effects on cultured motoneurons. Using in situ hybridization, we found a differential expression of group I mGluRs (mGluR1 and 5) in rat spinal cord. Autonomic motoneurons from the sacral parasympathetic Onuf's nucleus and thoracic sympathetic neurons, which are spared in ALS, express high levels of mGluR5, while somatic motoneurons do not. In addition, mGluR1 mRNA is found only in smaller somatic motoneurons, which seem to be less vulnerable in ALS. Thus, differential mGluR expression might provide a possible clue to the selective vulnerability of different motoneuronal subpopulations in ALS.

Ultrastructural identification of substance P containing nerves in the guinea pig trabecular meshwork.

We aimed to provide a detailed analysis of substance P (SP)-containing nerves in the trabecular meshwork by ultrastructural immunohistochemistry and capsaicin treatment for chemical ablation of the sensory nerves. Numerous myelinated and unmyelinated nerves were observed inside the sheets and intertrabecular spaces of the trabecular meshwork, and the inner side of Schlemm's canal. SP-like immunoreactive products were identified in some of these nerves and associated with numerous vesicles of different sizes, a few mitochondria and numerous neurotubili. After the capsaicin treatment, SP-like immunoreactive nerves persisted and no degenerated SP-like immunoreactive nerves were noted. On the basis of the ultrastructural features and the results of capsaicin treatment, it seems that these nerves are most probably autonomic in origin. Autonomic efferent SP-containing nerves are confirmed directly located in the trabecular meshwork; these have not been previously described at electron microscopic level. SP in autonomic efferent nerves might act as a neurotransmitter or neuromodulator for intraocular pressure regulation.