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E R Tamm

Publications and source records attributed to E R Tamm.

18 recordsLinked to original sources

Characterization of the mouse Myoc/Tigr gene.

Mutations in the myocilin (MYOC), also known as Trabecular meshwork-Inducible Glucocorticoid Response (TIGR) gene can lead to juvenile open-angle glaucoma in human and may be responsible for at least 3% of primary open-angle glaucoma. To develop a mouse model of primary open angle glaucoma, and to get deeper insight into the mechanisms of the MYOC/TIGR gene regulation and function, we have isolated and characterized full size mouse Myoc/Tigr cDNA and genomic clones. The mouse and human MYOC/TIGR genes have the same exon-intron structure and contain 3 exons, although the mouse gene is 6 kb shorter than the human gene (10 kb versus 16 kb) due to differences in the length of introns. The MYOC/TIGR gene encodes a moderately conserved protein, which is 82% identical between human and mouse. The encoded protein is 14 amino acids shorter at the N-terminus in the mouse than in the human (490 versus 504 amino acids). Mouse and human MYOC/TIGR genes show a similar pattern of expression in adult ocular and nonocular tissues. The mouse Myoc/Tigr gene was mapped to Chromosome 1 at position 82.8 cM from the centromere. All residues, which were identified in the human MYOC/TIGR protein as critical for glaucoma development, are conserved in the mouse Myoc/Tigr.

Adult

Effects of transforming growth factor-beta1 and basic fibroblast growth factor on proliferation of cell cultures derived from human vestibular nerve schwannoma.

The influence of transforming growth factor-beta1 (TGF-beta1) and basic fibroblast growth factor (bFGF) on growth of cell cultures derived from unilateral vestibular nerve schwannomas was investigated. Cell cultures were initiated from 9 schwannomas and characterized immunocytochemically with antibodies against S-100 and type IV collagen. The effects of TGF-beta1 and bFGF on DNA synthesis in chemically defined serum-free medium were assessed by measuring the incorporation of 5-bromo-2'-deoxy-uridine (BRDU) into cellular DNA. Cell proliferation was evaluated with an electronic cell counter. Reverse transcription polymerase chain reaction (RT-PCR) was performed using oligonucleotide primers specific for TGF-beta1 and TGF-beta2. TGF-beta1 stimulated DNA synthesis in a dose dependent manner. Maximal stimulation was observed at a concentration of 1 ng/ml, which induced a nearly 2-fold increase in DNA content. This effect was not seen when TGF-beta1 was added in the presence of neutralizing antibodies. In addition, antibodies against TGF-beta1 significantly reduced DNA synthesis in control cultures without supplemented exogenous growth factors. bFGF alone had no significant effects on DNA synthesis. In contrast, when TGF-beta1 and bFGF were added together, the mitogenic response was much greater than produced by TGF-beta1 alone. RT-PCR showed that the cultured cells expressed mRNA for both TGF-beta1 and TGF-beta2. We hypothesize that TGF-beta1 is an autocrine growth factor for human vestibular nerve schwannomas in culture. A similar mechanism might be involved in the growth of these tumors in situ.

Adult

Superior cervical ganglionectomy in monkeys: light and electron microscopy of the anterior eye segment.

Morphological changes in the anterior eye segment of eight cynomolgus monkeys were investigated 2 days to 2.2 years after unilateral surgical superior cervical ganglionectomy (SCGx). SCGx was confirmed by histologic examination of the excised surgical specimen and persistent ipsilateral miosis. In four short-term monkeys (2, 4, 7 and 11 days), iris, ciliary muscle and trabecular meshwork were studied by electron microscopy. In the other four longer-term monkeys (3 week, 4 week, 5 week, 2.2 year) the anterior eye segment was investigated with tyrosine hydroxylase immunohistochemistry (TH-IR) and catecholamine fluorescence (CF). Electron microscopy of experimental eyes showed characteristic signs of Wallerian degeneration in numerous nerve fibers and terminals in the iris, but to a lesser extent in the ciliary muscle and the trabecular meshwork. TH-IR and CF showed marked interindividual differences. In all experimental eyes, there was a marked reduction, but never a complete absence of adrenergic nerves in the iris. In two animals (4 week and 2.2 years), the adrenergic innervation of the ciliary body and the chamber angle was similarly reduced. In contrast, in the experimental eyes of the other two animals (3 and 5 weeks), changes in adrenergic innervation to the ciliary body and chamber angle were minimal or absent. The results indicate that following apparently complete SCGx in the cynomolgus monkey, reduction of adrenergic innervation to the iris as evidenced by pupillary physiology, electron microscopy, TH-IR and CF does not guarantee reduction in adrenergic innervation to the ciliary body and trabecular meshwork. SCGx may not extirpate all third order sympathetic neurons in the distal stump, or there may be a significant contribution of accessory ganglion cells to the adrenergic innervation of the anterior eye segment.

Adrenergic Fibers

Nitrergic nerve cells in the primate ciliary muscle are only present in species with a fovea centralis.

Nerve cells positive for NADPH diaphorase (D)/nitric oxide synthase in the human ciliary muscle appear to be involved in relaxation of the muscle during disaccommodation. To study whether similar cells might mediate disaccommodation of the primate ciliary muscle in general, serial sections of the ciliary muscle of 5 cynomolgus monkeys (Macaca fascicularis) and 2 owl monkeys (Aotes trivirgatus) were stained for NADPH-D. Both monkey species have a ciliary muscle system and an accommodative amplitude comparable to that in humans. Positively stained cells were frequently observed in the ciliary muscle of all cynomolgus monkeys, a diurnal species with a fovea, but never in owl monkeys, a nocturnal species without a fovea. The results indicate that NADPH-D-positive and probably nitrergic ganglion cells in the ciliary muscle are not present in all primate species, but only in those with high requirements for visual acuity. They might smoothen the ciliary-ganglion-mediated contraction of the ciliary muscle or contribute to the small fluctuations or oscillations of accommodation that are observed under steady viewing conditions.

Accommodation, Ocular

Ciliary body.

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Cell Communication

Transforming growth factor-beta 1 induces alpha-smooth muscle-actin expression in cultured human and monkey trabecular meshwork.

Transforming growth factor-beta 1 (TGF-beta 1) induces alpha-smooth muscle (sm)-actin expression and a contractile myofibroblast-like phenotype in a considerable number of different cell types. Since alpha-sm-actin is expressed in some of the resident human trabecular meshwork (TM) cells in situ, and TGF-beta 1 is synthesized by TM in vitro, alpha-sm-actin expression in TM might also be under the influence of TGF-beta 1. To assess this question, TM cultures were initiated from the eyes of three human donors and three cynomolgus monkeys. Various doses of TGF-beta 1 (0.5-5 ng ml-1) were added to confluent cultures from third to fourth passages. Experiments were performed in the presence of fetal calf serum or under chemically defined serum-free conditions. Four days after treatment, cells were stained immunocytochemically for alpha-sm-actin, and the number of positively labelled cells was quantitatively evaluated. In addition, reverse transcription polymerase chain reaction (PCR) was performed using oligonucleotide primers specific for alpha-sm-actin. In control cultures supplemented with serum, 19.0 +/- 9.4% of human meshwork cells, and 10.2 +/- 4.5% of monkey meshwork cells expressed immunoreactivity for alpha-sm-actin. In human cultures, this number was significantly higher in serum-free conditions (34.1 +/- 7.7%). Treatment with TGF-beta 1 induced alpha-sm-actin expression in a dose-dependent manner. At 5 ng ml-1 TGF-beta 1, 75.5 +/- 7.1% of human meshwork cells expressed distinct stress fibers that stained positively for alpha-sm-actin (P < or = 0.01). A similar albeit smaller increase in alpha-sm-actin positive cells was observed in monkey cultures following treatment with TGF-beta 1. These effects were seen with and without serum, but not when TGF-beta 1 was supplemented in the presence of neutralizing antibodies. In PCR experiments, a distinct product was amplified with cDNA derived from cells treated with 0.1 ng and 1 ng ml-1 TGF-beta 1, but not in control cultures. We conclude that TGF-beta 1 may play a role in differentiating TM cells towards a myofibroblast-like cell type by modulating the expression of alpha-sm-actin.

Actins

Gap junctions are found between iris sphincter smooth muscle cells but not in the ciliary muscle of human and monkey eyes.

Physiological studies indicate that in primate ciliary muscle there is little or no spread of electrical activity from cell to cell. To clarify to what extent primate intraocular smooth muscles express the structural correlate of electrical coupling, the localization of gap junctions in the ciliary and the iris sphincter muscle of human and monkey (Macaca fascicularis) eyes was analysed using electronmicroscopy and connexin43 immunocytochemistry. With both methods, numerous gap junctions were identified in the iris sphincter of both species, while no such junctions were observed between individual smooth muscle cells in the ciliary muscle. Both ciliary and iris sphincter smooth muscle cells were connected by numerous adherens-type junctions. These results further underline that primate ciliary muscle is an atypical smooth muscle which shares many common features with striated skeletal muscle.

Aged

Characterization of Meibomian gland innervation in the cynomolgus monkey (Macaca fascicularis).

To characterize the innervation of the cynomolgus monkey (Macaca fascicularis) Meibomian (tarsal) glands, upper lids of six cynomolgus monkeys were investigated with electronmicroscopical and double-labeling immunocytochemical methods. Antibodies against calcitonin gene-related peptide (CGRP), dopamine-beta-hydroxylase (DBH), neuropeptide Y (NPY), nitric oxide synthase (NOS), protein gene product 9.5 (PGP 9.5), substance P (SP), tyrosine hydroxylase (TH), and vasoactive intestinal peptide (VIP) were used. In addition, sections were processed for NADPH-diaphorase (NADPH-d) histochemistry. Staining for PGP 9.5 and electron microscopy showed that Meibomian gland acini were surrounded by a network of unmyelinated nerves and terminal varicose axons. The terminals contained small agranular (30-60 nm) and large granular vesicles (65-110 nm), and were observed in close contact with the basal lamina of the acini, but never internally to the basal lamina. Meibomian axons showed like-immunoreactivity (LI) for the neuropeptides SP, CGRP, NPY, and VIP. In addition, the axons stained for TH, DBH, NOS, and NADPH-d. VIP-LI, NOS- and NADPH-d-positive axons appeared to be more numerous, TH- and DBH-positive axons more rare than others. Most SP-LI axons were double-labelled for CGRP-LI, some for VIP-LI or NPY-LI. In addition, some VIP-LI axons were double-labeled for NPY-LI. NPY/VIP-LI and NPY/SP-LI axons were only observed close to the Meibomian acini. Conversely, NPY-LI colocalized with TH-IR or DBH-IR predominated in perivascular nerves of Meibomian gland vasculature. The close association of varicose axons with the acini of Meibomian glands indicates that nervous signals modulate meibomian secretion. Meibomian gland nerve fibers in the cynomolgus monkey appear to utilize various neuropeptides, catecholamines and nitric oxide as transmitter substances, and seem to derive from the pterygopalatine, superior cervical and trigeminal ganglion respectively.

Animals

Carbonic anhydrase activity is increased in retinal pigmented epithelium and choriocapillaris of RCS rats.

BACKGROUND: In Royal College of Surgeons (RCS) rats the retinal pigmented epithelium (RPE) exhibits defective phagocytosis of rod outer segments, causing degeneration of the photoreceptor layer. It is not known whether another function of the RPE, ion and fluid transport, is also affected by the disease. One enzyme involved in modulation of RPE transport activities is carbonic anhydrase (CA). To clarify whether changes in CA activity are correlated with the process of retinal degeneration, the localization of CA activity in RCS rat eyes was investigated. METHODS: Eyes of 12 RCS rats and 12 age-matched congenic controls of different ages were studied, using a modified histochemical method of Hansson for light and electron microscopy. RESULTS: Control eyes showed CA staining in corneal endothelium, both layers of ciliary epithelium, Müller cells, inner segments of photoreceptors, and RPE cells. In RPE the apical membranes were most intensely stained. In RCS rats, changes in CA staining were seen only in the posterior segment of rats 6 and 7 months of age. Most of the RPE cells were more intensely stained than those of age-matched controls, especially due to increased CA activity in the basolateral membrane infoldings. Adjacent endothelial cells of the choriocapillaris and of retinal capillaries developed staining for CA activity. CONCLUSION: Changes in CA activity in the RPE and adjacent capillary endothelium, together with previously described changes in RPE morphology in RCS rats, indicate changes in ion and fluid transport across the RPE. Since the retina was already impaired when the increase in CA activity occurred, we hypothesize that the causative factor is not the genetic defect per se, but the destruction of the retina.

Animals

Ocular adenovirus gene transfer varies in efficiency and inflammatory response.

PURPOSE: To study the effects of adenoviral gene transfer to the tissues of the anterior segment in vitro by rat and monkey lens organ cultures and in vivo by single injection into the anterior chamber of rabbits. METHODS: In vitro, intact lens cultures were exposed to 1 to 4 x 10(8) pfu Av1LacZ4 and Av1Luc1 in TC199 medium containing no serum or growth factors. Av1LacZ4 and Av1Luc1 are replication-deficient adenovirus vectors, carrying the reporter genes Escherichia coli LacZ and firefly luciferase, respectively. In vivo, the anterior chambers of eight rabbits were injected once with 20 mumol Av1LacZ4 (8 x 10(8) pfu) and evaluated 48 hours after injection. Enzyme activity of the reporter genes was measured biochemically and histochemically. RESULTS: In organ cultures, adenovirus delivers reporter genes efficiently to the ciliary processes but penetrates poorly into the capsulated lenses. Viral receptors, however, are present in rat lens epithelium, as in primary trabecular meshwork and other lens cell lines. In vivo, gene transfer was evident in corneal endothelium, iris anterior surface, and trabecular meshwork. Presence of the virus did not affect lens transparency or provoke external discomfort signs. Infected corneal endothelial cells were swollen and partly detached; 3 of 8 infected eyes showed a severe inflammatory response in chamber angle, anterior uvea, and limbal conjunctiva. CONCLUSIONS: These findings reveal the distinct gene transfer potential of each of the tissues of the anterior segment and emphasize the need to address the inflammatory response to these first-generation adenoviral vectors.

Adenoviruses, Human

Human and monkey trabecular meshwork accumulate alpha B-crystallin in response to heat shock and oxidative stress.

PURPOSE: Oxidative stress and other forms of injury to trabecular meshwork (TM) cells may contribute to changes seen with age and primary open-angle glaucoma. This study was designed to investigate if TM expresses alpha B-crystallin, a small heat-shock protein with chaperone activity, and whether it might be overexpressed under stress conditions. METHODS: The TM from human and monkey eyes, as well as organ and primary cell cultures derived from these eyes, were investigated for alpha B-crystallin by immunohistochemistry, two-dimensional gel electrophoresis, Northern and Western blot analysis. The TM cell cultures were stressed by heat shock (44 degrees C for 15 minutes) or hydrogen peroxide (200 mumol for 1 hour). Semiquantitation of alpha B-crystallin messenger RNA (mRNA) or protein was obtained by densitometry. RESULTS: In both species, alpha B-crystallin could be detected in fresh and cultured TM by two-dimensional gel electrophoresis in conjunction with Western blot analysis. Immunohistochemistry of fresh samples showed that alpha B-crystallin was expressed predominantly in the cribriform area. Protein expression was enhanced in 4- to 7-day organ cultures. Primary cultures from human TM cells expressed two sizes (approximately 0.8 and 1.1 kb) of alpha B-crystallin mRNA in Northern blots. In monkey TM cultures, a 0.8-kb band was observed, which comigrated with lens alpha B-crystallin. In both species, heat shock caused a significant increase in alpha B-crystallin mRNA with a peak after 4 hours. An increase in alpha B-crystallin mRNA also was observed after oxidative stress; however, the onset of mRNA induction was slower. After heat shock, but not after oxidative stress, a transient change in mRNA mobility was observed. Western dot blot analysis showed a 3.4-fold increase in protein 24 hours after heat shock and a 20-fold increase after 48 hours. No constitutive mRNA expression and only a minimal increase 4 hours after heat shock could be observed in simian virus 40 transformed cell lines from human TM. CONCLUSIONS: Overexpression of alpha B-crystallin might be an important mechanism for TM to prevent cellular damage associated with various stress conditions.

Aged

Immunohistochemical localization of neuropeptides in the human ciliary ganglion.

In human ciliary ganglia, 18% of neurons were in contact with substance P (SP) and 12% with calcitonin gene-related peptide (CGRP) like-immunoreactive (LI) varicose axons. CGRP was colocalized with SP. Numerous SP-LI and CGRP-LI non-varicose nerve fibers were found between the ganglion cells and in nerve trunks that entered the ganglia. Axons immunoreactive for neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), tyrosine hydroxylase (TH) or dopamine-beta-hydroxylase (DBH) never contacted neuronal cell bodies. Perikarya of ciliary neurons neither stained for any of the neuropeptides nor for DBH. 23% of ciliary perikarya were TH-immunoreactive. These observations suggest an innervation of human ciliary ganglion neurons by peptidergic primary afferent collaterals presumably of trigeminal origin.

Adult

Laminin promotes differentiation, adhesion and proliferation of cell cultures derived from human acoustic nerve schwannoma.

The influence of laminin on cell cultures derived from unilateral acoustic nerve schwannomas was investigated. Cell cultures were initiated from 12 schwannomas, removed via the enlarged middle cranial fossa approach. Tumor tissue was dispersed by collagenase treatment and cells seeded in uncoated or laminin-coated culture dishes. Confluent cultures were immunocytochemically characterized with antibodies against S-100, CD 68, factor VIII-related antigen and type IV collagen. Cell adhesion in response to different doses of laminin was evaluated with an electronic cell counter. The effect of laminin on cell proliferation was assessed by measuring the incorporation of 5-bromo-2'-deoxy-uridine (BRDU) into cellular DNA. Cells cultured on laminin as substrate appeared more differentiated with long, fusiform, cytoplasmic processes. Cultured cells stained positive for S-100, not for factor VIII-related antigen or CD 68. Only cells cultured on laminin deposited a dense extracellular network of type IV collagen. When laminin was added to the culture medium, cell attachment and proliferation was stimulated in a dose dependent manner. Maximal stimulation of both was observed with a laminin concentration of 50 micrograms/ml, which induced a nearly 2-fold increase in cell attachment and an approximately 66% increase in DNA content. Since laminin is a major component of the extracellular matrix in schwannomas, the possibility exists that laminin is also mitogenic for human neoplastic Schwann cells in situ.

Adult

Nerve cells in the human ciliary muscle: ultrastructural and immunocytochemical characterization.

PURPOSE: Intrinsic nerve cells in the human ciliary muscle were identified and characterized by immunohistochemical and ultrastructural methods. METHODS: Serial sections through the ciliary muscle of 10 human donors (age range, 53 to 91 years) were investigated by electron microscopy, NADPH-diaphorase (NADPH-d) staining, and immunohistochemistry. Antibodies against nitric oxide synthase (NOS), protein gene product 9.5 (PGP 9.5), neurofilament proteins, tyrosine hydroxylase (TH), neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), substance P (SP) and calcitonin gene-related peptide (CGRP) were used. Nerve cell density per millimeter of circumferential width was analyzed in three eyes, and in one eye the total number of neurons in the entire ciliary muscle was evaluated. RESULTS: Small (70% of the total; longitudinal diameter 10 to 14 microns) and large (longitudinal diameter 20 to 30 microns) ganglion cells were identified in the inner parts of the muscles' reticular and circular portions. No nerve cells were observed in the anterior longitudinal portion. The cells were in contact with unmyelinated axons and synaptic boutons containing small agranular and large granular vesicles. Axo-somatic and axo-dendritic synapses were observed. Histochemically and ultrahistochemically, the neurons stained intensely for NADPH-d. Both cell types were multipolar and expressed long filamentous processes. Axonal processes with periodic swellings suggesting varicosities ran close and parallel to neighboring muscle bundles. Some nerve cells were connected with each other by axonal processes. No perivascular NADPH-d-positive nerves were seen around ciliary muscle vessels, but they were present in the wall of the major arterial circle of the iris. A small number of ganglion cells contributed to this perivascular network. NADPH-d-positive neurons stained for PGP 9.5 and NOS. No TH, NPY, or VIP-positive ciliary muscle neurons were observed. In double labeling experiments, 70% of the nerve cells were in contact with nerve endings expressing SP-like and CGRP-like immunoreactivity. Seventeen to 32 NADPH-d-positive neurons were counted per millimeter of ciliary muscle circumferential width, with 923 in the entire ciliary muscle of one donor eye. CONCLUSIONS: The presence of intrinsic NOS-positive nerve cells concentrated in the inner parts of the ciliary muscle might indicate a physiological role of nitric oxide for disaccommodation or fluctuations during accommodation.

Aged

Innervation of myofibroblast-like scleral spur cells in human monkey eyes.

PURPOSE: To study the innervation of the presumably contractile, myofibroblast-like scleral spur cells in human and cynomolgus monkey eyes. METHODS: Serial tangential sections of the scleral spur region of the eyes of 16 human donors and 6 cynomolgus monkeys were investigated with immunocytochemical methods. Antibodies against acetylcholinesterase, synaptophysin, alpha-smooth muscle actin, calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), nitric oxide synthase (NOS), substance P (SP), tyrosine hydroxylase (TH), and vasoactive intestinal peptide (VIP) were used. In addition, sections were processed for glyoxylic acid-induced catecholamine fluorescence (CF) and for NADPH-diaphorase (NADPH-d). RESULTS: In the eyes of both species, circumferentially oriented varicose axons were observed in the scleral spur region of all quadrants. Double labeling showed that most of these scleral spur axons were in close contact with the alpha-smooth muscle actin-positive, myofibroblast-like scleral spur cells. In human eyes, the axons showed like-immunoreactivity (LI) for SP, CGRP, NPY, VIP, and NOS. In addition, numerous scleral spur axons stained for NADPH-d. Most SP-LI scleral spur axons were double-labeled for CGRP-LI, and none for VIP-LI. All NPY-LI scleral spur axons were double labeled for VIP-LI but lacked immunoreactivity to TH. Some VIP-LI axons were not labeled for NPY-LI. Nerve fibers immunoreactive (IR) for TH or positively stained for CF were not observed in association with scleral spur cells. In contrast, in cynomolgus monkey eyes, circumferentially oriented TH-IR and CF-positive varicose axons were observed frequently in the scleral spur region. In addition, SP-LI, CGRP-LI, and NPY-LI/TH-IR axons were present in the chamber angle of monkey eyes, whereas VIP-LI, VIP-LI/NPY-LI, NOS-positive, or NADPH-d-positive nerve fibers were absent. In both species, positive staining for acetylcholinesterase was seen only in the ciliary muscle, not in the scleral spur region. CONCLUSIONS: The close association of varicose axons with the myofibroblast-like scleral spur cells indicates that nervous signals modulate scleral spur cell tone. A sympathetic scleral spur cell innervation is present only in cynomolgus monkeys but seems to be absent in humans. Conversely, scleral spur axons of presumably parasympathetic origin (NOS-IR or NADPH-d-positive, VIP-LI, and VIP-LI/NPY-LI) are absent in the cynomolgus monkeys but present in humans. In both species, a cholinergic innervation of the scleral spur cells seems to be rare or absent.

Adult

Species differences in choroidal vasodilative innervation: evidence for specific intrinsic nitrergic and VIP-positive neurons in the human eye.

PURPOSE: There is evidence that vasodilation of choroidal vessels results from facial nerve stimulation. To obtain more information about the role of this innervation, the authors examined the presence and spatial organization of nitrergic and vasoactive intestinal peptide (VIP) immunoreactive nerves in the human choroid. For comparison, the choroid of rabbit and rat eyes, with different types of retinal vascularization and no fovea, were studied. METHODS: Whole mounts of five human, nine rat, and two rabbit choroids were stained for NADPH-diaphorase. In addition, immunocytochemical staining was carried out on tangential frozen sections of two human choroids using antibodies against nitric oxide synthase (NOS), synaptophysin, and VIP. RESULTS: In all species, a perivascular network of diaphorase-positive nerve fibers with varicose terminals accompanied the arteries and arterioles of the choroidal stroma. A striking difference to rat and rabbit choroids was the presence of numerous positively stained ganglion cells in human choroids. Positively stained axons connected the neurons with each other and with the perivascular network. Most of the ganglion cells were concentrated in the temporal-central region, adjacent to the fovea. Immunocytochemically, the choroidal ganglion cells were immunoreactive for NOS. Some ganglion cells stained for VIP. Staining for synaptophysin demonstrated varicose terminals innervating the perikarya of the ganglion cells. Many of these terminals stained for NOS and VIP. CONCLUSIONS: The presence of an intrinsic nerve cell plexus that is specifically localized in human eyes in the temporal-central portion of the choroid indicates a functional significance of the nitrergic choroidal innervation for the fovea.

Aged

Nerve endings with structural characteristics of mechanoreceptors in the human scleral spur.

PURPOSE: The innervation of the scleral spur region was investigated to learn whether mechano-receptors are present in this region. METHODS: Serial tangential sections and whole-mount preparations of the scleral spur region of 18 human eyes of different ages were investigated with electronmicroscopic and immunohistochemical methods. For immunohistochemistry antibodies against neurofilament-proteins, synaptophysin, substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), tyrosine-hydroxylase, dopamine-beta-hydroxylase, and acetylcholinesterase were used. RESULTS: Club- or bulb-shaped nerve endings with a diameter of 5 microns to 25 microns were identified in the scleral spur region throughout the whole circumference of the eyes. The terminals derive from myelinated axons with a diameter of approximately 3 microns and stain with antibodies against neurofilament-proteins and synaptophysin but do not stain for tyrosine-hydroxylase, dopamine-beta-hydroxylase, acetylcholinesterase, NPY, VIP, SP, or CGRP. Electronmicroscopically, the endings contain abundant neurofilaments, granular and agranular vesicles of different sizes, numerous mitochondria, and lysosome-like lamellated structures. The endings are incompletely ensheathed by Schwann cells. Those areas of the cell membrane of the endings that are not covered by Schwann cells are in intimate contact with the fibrillar connective tissue elements of the scleral spur. CONCLUSION: These structural features are highly characteristic for mechanoreceptive nerve endings in other tissues of the human body. The authors therefore hypothesize that the club-or bulb-shaped nerve endings in the human scleral spur are afferent mechanoreceptors that measure stress or strain in the connective tissue elements of the scleral spur. Such changes might be induced by ciliary muscle contraction and/or by changes in intraocular pressure.

Adult