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PubMed2002

A goniolens for clinical monitoring of the mouse iridocorneal angle and optic nerve.

PURPOSE: Due to the increasing importance of mouse models and mouse genetics in ophthalmic research, we have developed a goniolens for mice. METHODS: The size and basic design parameters of a human goniolens were adapted to the mouse eye. RESULTS: The goniolens is straightforward to use and allows non-invasive visualization of the structures of the anterior chamber angle, including Schlemm's canal, trabecular meshwork, iris and anterior surface of the peripheral ciliary body. Goniophotography using the mouse lens allows documentation of anterior chamber angle abnormalities, and facilitates comparisons of changes to these structures in the same eye over time. In addition, high quality magnified views of the optic nerve, retinal vessels and posterior retina are easily obtained. CONCLUSIONS: This goniolens is an important new tool for studying the genetic and clinical etiology of anterior segment dysgenesis and glaucoma in mice.

Animals↗
PubMed1985

Substance P-like immunoreactive nerves in the human eye.

Using immunohistochemical methods, substance P is localized to nerves of the human eye. Immunoreactive nerve fibers occur in the cornea, about limbal blood vessels, and within the trabecular meshwork. Substance P-like immunoreactive nerve fibers surround uveal blood vessels, especially in the choroid and ciliary body. Immunoreactive nerves are seen in ciliary processes. The ciliary muscle is innervated, as are the iris dilator and sphincter muscles. Apposition of immunoreactive nerves to uveal melanocytes is apparent. The distribution of substance P-like immunoreactive nerves in the human eye parallels that found in other mammals. While substance P probably has important neurotransmitter or neuromodulator roles in the eye, further physiologic studies are required to define its ocular function.

Adolescent↗
PubMed1986

Histopathology of abnormalities of the anterior chamber with glaucoma.

Neural crest cells give rise to all connective tissues anterior to the lens epithelium including corneal stromal cells, corneal and trabecular mesothelial cells, iris stromal cells, and iris melanophores. These cells constitute a continuous layer which extends from the corneal mesothelium to trabecular meshwork mesothelium and onto the anterior surface of the iris. Between the seventh and eighth month of gestation in man, the layer of cells loses its continuity. The present case suggests a defective terminal induction of a particular structural component of the angle derived from neural crest resulting in massive congenital adhesions in the anterior chamber angle. The persistence of a layer of abnormal cells lining the anterior chamber structures further reinforces the presence of defective mesothelial cells. Additional cases having such clinicopathologic correlation may provide further insight into this hypothesis.

Adult↗
PubMed1997

CHARGE association with congenital glaucoma due to maldevelopment of the anterior chamber angle.

PURPOSE: We examined the clinicopathologic features of a male infant with the CHARGE association and bilateral congenital glaucoma. METHODS: Trabeculectomy specimens were obtained from the anterior chamber angle and examined by light and electron microscopy. RESULTS: Histopathologic examination of the trabeculectomy specimens showed immature development of the trabecular meshwork that was covered by the ciliary muscles. There were few intertrabecular spaces because the meshwork was almost completely filled with cells and extracellular substances. Deposition of a granular and/or homogeneous substance was observed in the subendothelial area of Schlemm's canal. CONCLUSIONS: Our patient exhibited features typical of the CHARGE association, but also had congenital glaucoma. We hypothesize that these clinical findings are all mediated by a neurocristopathic mechanism. Our findings suggest that the CHARGE association may predispose to anterior chamber angle maldevelopment, which can lead to congenital glaucoma.

Abnormalities, Multiple↗
PubMed2001

Role of tissue growth factors in aqueous humor homeostasis.

The aqueous humor supplies nutrients to the nonvascularized cornea, lens, and trabecular meshwork. A number of tissue growth factors have been detected in this fluid. The composition of these proteins changes dramatically with different ocular conditions, such as inflammation and glaucoma. In this review, an overview of new findings regarding effects of aqueous humor growth factors is given. Our main emphasis is on the regulation of the avascular anterior eye compartment, the possible role of growth factors in the pathogenesis of glaucoma, and the importance of growth factors for the special immunosuppressive status of the anterior chamber.

Animals↗
PubMed2005

Substance P and opioid peptidergic innervation of the anterior eye segment of the rat: an immunohistochemical study.

Recently discovered endogenous opioid peptides such as nociceptin are known to modulate neurotransmitter release of primary afferent neurons (especially substance P, SP) and they have also been demonstrated in peripheral nerve fibres. The aim of this study was to investigate the opioid peptidergic innervation of the anterior eye segment and to compare it with the innervation pattern of SP in order to shed light on the functional relationship between these peptides. Anterior eye segments of 20 rat eyes were cut in a tangential plane and the sections stained with antibodies against SP, nociceptin, nocistatin, endomorphin 1 and 2, leu-enkephalin and met-enkephalin. Sections of the spinal cord or brain were used as positive controls. Numerous SP-immunoreactive nerve fibres were found in the conjunctiva, cornea, episclera, trabecular meshwork, iris and ciliary body. A weak staining for met-enkephalin and leu-enkephalin could only be found in the iris and anteriormost ciliary body. Nerve fibres immunoreactive for nociceptin, nocistatin, and endomorphin 1 or 2 could not be detected in any part of the anterior eye segment. It is tempting to speculate that the opioid peptidergic innervation of the anterior ciliary body may play a role in the modulation of intraocular inflammation.

Animals↗
PubMed1994

Immunohistochemical localization of transforming growth factor-beta 1, -beta 2, and -beta 3 latency-associated peptide in human cornea.

PURPOSE: To study spatial distribution of TGF-beta isoforms (TGF-beta 1, -beta 2, and -beta 3) in the human cornea and to elucidate their biologic roles in corneal maintenance. METHODS: Frozen sections obtained from eight human autopsy eyes were placed on gelatin-coated slides. After blocking of nonspecific binding sites, the slides were incubated with rabbit polyclonal antibody to the latency-associated peptide (LAP) region of human TGF-beta 1, TGF-beta 2, and TGF-beta 3 precursors, followed by the incubation with biotinylated swine anti-rabbit IgG. Subsequently, a streptavidin-labeled alkaline phosphatase technique was used. RESULTS: In the corneal region, beta 1-LAP antibody did not stain either epithelium or stroma, beta 2-LAP antibody stained all epithelial cell layers and the corneal stroma, and beta 3-LAP antibody stained the subepithelial region alone. The staining pattern in the limbal region was almost the same as in the corneal region, except in the limbal stroma, which was stained with beta 1-LAP antibody in three of eight samples. In the trabecular meshwork, all samples showed clear staining with beta 2-LAP antibody, whereas beta 1-LAP and beta 2-LAP antibody stained faintly in five of eight and four of eight samples, respectively. CONCLUSION: beta 2-LAP was found in the corneal epithelium and stroma and beta 3-LAP in the subepithelial region, suggesting that TGF-beta 2 and TGF-beta 3 may play essential roles in normal corneal epithelial maintenance in vivo.

Adult↗
PubMed1984

Corneal endothelial overgrowth of angle and iris. Evidence of myoblastic differentiation in three cases.

Corneal endothelialization of the anterior chamber angle was observed in three cases of iris neovascularization and one case of post-contusion deformity. Scanning electron microscopy in two cases revealed a sheet composed of confluent fusiform cells forming a regular mosaic, growing in a tissue culture-like fashion, and extending over the anterior iris surface. Electron microscopy revealed an endothelial lining continuous with the corneal endothelium extending over the fibrovascular membrane which covered the anterior iris surface in the cases of iris neovascularization and partially extended over the trabecular meshwork in an eye with post-contusion deformity. These endothelial cells possess junctional complexes, apical villi, and prominent basement membrane. In addition, myoblastic differentiation with intracytoplasmic microfilaments, measuring 5 to 6 nm in diameter and often marginally located with fusiform densities, were observed. The presence of myoblastic features may play a role in the ability of corneal endothelial cells to migrate and participate in production of peripheral anterior synechia and ectropion of the iris.

Adolescent↗
PubMed1994

Corticosteroids enhance S-antigen expression in nonretinal ocular tissues of rats with experimental autoimmune uveitis.

S-antigen (S-Ag), a major protein on the retinal photoreceptor cell, can induce experimental autoimmune uveitis (EAU). We have previously detected S-Ag and its mRNA in irises of chronic uveitis patients receiving long-term steroid therapy. To further investigate the effect of steroid therapy on ocular tissue, we compared levels of S-Ag and its mRNA in EAU rats with and without steroid treatment. EAU was induced in 72 Lewis rats by two footpad injections of S-Ag. The rats were then treated with Depo-Medrol or phosphate-buffered saline by intramuscular injection. Eyes were collected at different time points. S-Ag mRNA was detected in the lens epithelium, trabecular meshwork, iris, and ciliary body of 47.2% of the steroid-treated group vs 22.2% of the controls. S-antigen was also detected in 30.6% of the eyes of the treated group vs 16.7% of the controls. S-Ag and its mRNA was found only in the retina of normal rats. These results support the hypothesis that prolonged corticosteroid therapy in uveitic patients might enhance the expression of S-Ag in nonretinal ocular tissues and might contribute to the ocular side effects of corticosteroid.

Animals↗
PubMed1986

Neuropeptide Y and the innervation of the human eye.

Using the indirect immunohistochemical technique, neuropeptide Y as found in human ocular nerves. While limbal blood vessels were innervated and a few nerves were seen in the trabecular meshwork, the cornea proper contained no immunoreactive nerve fibers. Neuropeptide Y-like immunoreactive nerves supplied the iris dilator muscle and, to a lesser extent, the iris sphincter. Immunoreactive nerve fibers were present within the ciliary muscle and the ciliary processes. Neuropeptide Y-like immunoreactive choroidal nerve fibers were frequently associated with blood vessels. The apposition of immunoreactive nerve fibers and melanocytes occurred throughout the uvea. The distribution of neuropeptide Y-like immunoreactive nerves in the eye closely parallels the adrenergic innervation. Evidence linking neuropeptide Y to the ocular sympathetic innervation is discussed.

Adolescent↗
PubMed2004

H-7 effect on outflow facility after trabecular obstruction following long-term echothiophate treatment in monkeys.

PURPOSE: To determine whether H-7 can enhance outflow facility after trabecular meshwork obstruction by extracellular material that accumulates after long-term treatment of monkeys with the cholinesterase inhibitor echothiophate iodide (ECHO). METHODS: Cynomolgus monkeys were treated topically with 150 microg ECHO in one (n = 4 eyes) or both (n = 8 eyes) eyes for up to 48 weeks. Accommodation response to topical pilocarpine was monitored periodically. Outflow facility response to H-7 was measured by two-level constant pressure perfusion on three or four different occasions after intraocular pressure was elevated for 12 to 18 weeks. RESULTS: Long-term treatment with ECHO decreased the accommodative response to pilocarpine and increased intraocular pressure, as has been reported. Baseline outflow facility was decreased by 46% +/- 7% (n = 12, P < 0.001). H-7 partially restored baseline outflow facility measured during subsequent perfusions while ECHO treatment was continued. Concurrent H-7 enhanced outflow facility by 73% +/- 18% (n = 12, P < 0.005) beyond the same-day baseline in ECHO-treated eyes. Cessation of ECHO treatment further restored baseline outflow facility, and the outflow facility response to H-7. CONCLUSIONS: H-7 can enhance OF in the presence of trabecular obstruction produced by long-term ECHO treatment. This suggests that H-7 may be useful in treating glaucoma, even in the presence of accumulated plaque material that has been described previously.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1988

Immunohistochemical staining of the human anterior segment. Evidence that resident cells play a role in immunologic responses.

We examined human corneoscleral tissue for cells that are phenotypically similar to known antigen-presenting cell (APC) populations. Antigen-presenting cells are involved in the uptake and processing of antigen for presentation to T lymphocytes, thereby playing a central role in induction of the immune response. The recognition of antigen by T lymphocytes requires that an APC express major histocompatibility complex class II molecules. Using immunoperoxidase staining techniques, the presence of cells expressing class II glycoproteins and T-cell subsets were determined. The staining patterns of the trabecular meshwork, ciliary body, cornea/sclera, and conjunctive are described for monoclonal antibodies OKT6, OKM1, HLA-DR, and HLA-DQ, and T-cell markers OKT8, Leu-3a, and Leu-4. The results of the present study demonstrate that the anterior chamber contains a network of immunocompetent cells. The presence of a subpopulation of cells within the anterior chamber that express class II glycoproteins of the major histocompatibility complex suggests this tissue may play an important role in immune regulation within the eye.

Anterior Eye Segment↗
PubMed1980

Distribution of albumin in the normal monkey eye as revealed by Evans blue fluorescence microscopy.

Since intravenously injected Evans blue binds irreversibly to serum albumin, its distribution reflects albumin exchange between the intravascular and extravascular tissue compartments. In histologic specimens examined by fluorescence, microscopy, extravasated Evans blue--albumin complex was identified within the ciliary body and trabecular meshwork of normal monkey eyes. In eyes fixed by intra-arterial perfusion of fixative, no dye was identified in the choroid, retina, or optic nerve. With immersion fixation, however, some extravasation was seen in the choroid and adjacent optic nerve. In some specimens, the optic nerve was stained not only with material apparently leaking from the choroid but also from a breakdown of the blood-brain barrier in the major disc vasculature during the interval before fixative penetrates into the tissue. Perfusion fixation must be used to avoid this artifact, and freezing techniques would be even better.

Animals↗
PubMed1997

Ocular blood flow in experimental glaucoma: a study in cynomolgus monkeys.

Experimental glaucoma was induced in 1 eye of 6 cynomolgus monkeys by laser treatment of the trabecular meshwork. In 5 of the 6 monkeys the increased intraocular pressure (IOP) caused marked glaucomatous damage in the experimental eye. Ocular blood flow was determined with labeled microspheres 4 years after the laser treatment. IOP was regulated with an external reservoir. With the same perfusion pressure in both eyes no statistically significant difference was observed between the 2 eyes for total ocular blood flow or for blood flow through any of the ocular tissues. Total ocular blood flow was 343.5 +/- 61.4 mg/min (mean +/- SEM) in the control eye and 385.3 +/- 107.7 mg/min in the experimental eye.

Animals↗
PubMed1993

Aqueous outflow system in familial amyloidotic polyneuropathy, Portuguese type.

Familial amyloidotic polyneuropathy (FAP) is a hereditary disease which may present a wide range of ocular manifestations. Glaucoma is amongst the most serious complications of FAP. We report the results of ultrastructural study of the trabecular meshwork in a glaucomatous patient with the Portuguese form of FAP. This study showed that there was marked anatomical disruption of the uveoscleral, cornoscleral meshworks and juxtacanalicular tissue characterized by (a) accumulation of amyloid fibrils in the intertrabecular spaces; (b) degeneration of the endothelial cells; (c) homogeneous and/or multilayered plaques of basement membrane-like material loading the intertrabecular spaces or protruding to the lumen of the Schlemm's canal; and (d) degeneration of unmyelinated nerve fibres. These morphological changes and an analysis of the literature suggest that mechanical and neuropathic events can be co-existing factors which enhance the resistance to aqueous humour outflow, leading to increased intraocular pressure and glaucoma in the Portuguese form of FAP.

Adult↗
PubMed2000

Reporter LacZ gene transfer into cultured ocular cells of human eyes in vitro.

OBJECTIVE: To investigate whether a reporter LacZ gene could be transferred into cultured ocular cells of human eyes in vitro. METHODS: Fibroblast cells of Tenon's capsule, trabecular meshwork cells, and muscle cells in the ciliary body of human eyes were cultured and the pcDNA3-LacZ gene was transferred into these cells using a cationic liposome delivery system. The cells were subsequently fixed with 4% paraformaldehyde, mixed with X-gal, then observed under a microscope. RESULTS: Blue stain was seen in the cytoplasm of the cultured cells under the microscope, demonstrating the successful transfer of the LacZ gene into these cells. CONCLUSION: Reporter LacZ gene was easily transferred into the cultured ocular cells in vitro. This provides insights into the transfer of the genes into these cells to study the pathogenesis and therapy of glaucoma.

Cells, Cultured↗
PubMed2006

Genotype and phenotype correlations in congenital glaucoma: CYP1B1 mutations, goniodysgenesis, and clinical characteristics.

PURPOSE: To determine whether there is a correlation among mutations in the cytochrome P4501B1 gene (CYP1B1), the degree of angle dysgenesis observed histologically, and disease severity in congenital glaucoma. DESIGN: Interventional case series. METHODS: Direct DNA sequencing was used to screen six unrelated children with congenital glaucoma, each set of parents, and all siblings for CYP1B1 mutations. Specimens of the anterior chamber angle obtained at trabeculectomy were examined histologically to identify abnormalities of the aqueous outflow pathway. CYP1B1 mutations were correlated with both the degree of angle dysgenesis and the patients' disease severity (age at diagnosis, difficulty in achieving intraocular pressure [IOP]) control. RESULTS: Four (66.7%) of the six patients were compound heterozygotes for mutations in the CYP1B1 gene. Seven of the eight CYP1B1 mutations were identified, including two novel mutations (R117P, C209R) and five others previously described (G61E, R368H, R390H, E229K, 4340delG). The cases were divided on the basis of histological phenotype into categories of (1) severe goniodysgenesis highlighted by the agenesis of the canal of Schlemm (two patients), (2) moderate goniodysgenesis characterized by the presence of a band of collagenous tissue (CT) in the trabecular meshwork (TM) and/or the juxtacanalicular tissues (JXT) (three patients), and (3) mild goniodysgenesis with deposition of a mucopolysaccharide material in the JXT (one patient). CYP1B1 mutations were identified in both cases of severe angle dysgenesis and two of three cases of moderate dysgenesis. Disease severity closely correlated with the degree of angle dysgenesis. CONCLUSIONS: Most patients in our cohort had compound heterozygous CYP1B1 mutations. Specific CYP1B1 mutations may be associated with severe or moderate angle abnormalities.

Anterior Chamber↗
PubMed1990

Pigmentary glaucoma in the black population.

The pigment dispersion syndrome is associated with a secondary open-angle glaucoma most commonly found in young, myopic, white males. We studied 20 cases (38 eyes) of pigment dispersion syndrome in black individuals as defined by heavy deposition on the corneal endothelium and trabecular meshwork with increased intraocular pressure but no other ocular abnormalities. The 20 patients were a homogeneous group that was typified by older age distribution (average, 73 years), a preponderance of hyperopia (median refraction, +2.15 diopters spherical equivalent), female gender (19 women, one man), no iris transillumination defects (zero of 38 eyes), and flatter iris insertion into the ciliary body. We believe that this homogeneous group of black individuals with pigment dispersion and atypical features represents a pigment dispersion syndrome associated with older age, hyperopia, and female sex preponderance, in the black race.

Adult↗