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PubMed1994

Genetic linkage of autosomal dominant juvenile glaucoma to 1q21-q31 in three affected pedigrees.

Glaucoma is a common disorder that results in irreversible damage to the optic nerve, causing absolute blindness. In most cases, the optic nerve is damaged by an elevation of the intraocular pressure that is the result of an abnormality in the normal drainage function of the trabecular meshwork. A family history of glaucoma is an important risk factor for the disease, suggesting that genetic defects predisposing to this condition are likely. Three pedigrees segregating an autosomal dominant juvenile glaucoma demonstrated significant linkage to a group of closely spaced markers on chromosome 1. These results confirm the initial mapping of this disease and suggest that this region on chromosome 1 contains an important locus for juvenile glaucoma. We describe recombination events that improve the localization of the responsible gene, reducing the size of the candidate region from 30 to 12 cM.

Adult↗
PubMed2001

Adenovirus-mediated gene therapy for corneal clouding in mice with mucopolysaccharidosis type VII.

Recent advances in systemic treatments for mucopolysaccharidosis have led to therapies that improve the multiple somatic features of this disease, but the therapeutic effect on ocular manifestations such as corneal clouding is not satisfactory. Here, we administered an adenovirus expressing human beta-glucuronidase (AxCAhGUS) into the anterior chamber or intrastromal region of the cornea in mice with mucopolysaccharidosis type VII (B6/MPSVII), and successfully treated corneal clouding of MPSVII. When we injected AxCAhGUS into the anterior chamber of the eyes, cells expressing beta-glucuronidase (GUSB) were located mainly in the trabecular meshwork as well as in all corneal regions, and subsequent pathological corrections in the cornea were achieved. Widespread transgene expression was also observed when we administered AxCAhGUS inside the cornea after lamellar keratotomy, and rapid elimination of the lysosomal storage in the corneal keratocytes occurred. Furthermore, intrastromal vector administration did not generate significant levels of anti-adenovirus neutralizing antibodies, and secondary vector administration was effective. Based on these observations, we conclude that it is worth developing a treatment strategy for corneal clouding in mucopolysaccharidosis based on direct intraocular administration of adenoviral vectors.

Adenoviridae↗
PubMed1992

The current management of herpetic eye disease.

Herpes simplex disciform keratitis is a difficult condition. The general feeling is that it is an immune disease, mediated by the virus, possibly located in the endothelial cells. It is frequently combined with inflammation in the trabecular meshwork and with uveitis. There is some controversy in relation to treatment and it has been suggested that anti-virals will control herpetic disciform keratitis, particularly if the patient has never had steroids previously. The authors of this paper have, in the past, published data which showed that Acyclovir, with corticosteroid, was necessary in the management of disciform keratitis. The data suggested that Acyclovir on its own was not effective. It remained to be answered whether Acyclovir on its own would be effective in patients who never had steroids for any reason previously. This paper demonstrates clearly that it is necessary, irrespective of whether patients have had steroids in the past or not, to combine corticosteroids with Acyclovir in the management of herpetic disciform keratitis. Acyclovir, on its own, is shown to be ineffective. It has also been suggested that Acyclovir is non-toxic. In a general way this is true, but the authors suggest that Acyclovir ointment does produce a punctate keratitis in patients with tear film disease, and that oral Acyclovir is preferable in such patients.

Acyclovir↗
PubMed1996

A complex interaction between topical verapamil and timolol on intraocular pressure in conscious rabbits.

Calcium channel blockers have complex actions on aqueous humour dynamics that seem to depend on the route of drug administration. When applied topically, verapamil and nifedipine effectively lower intraocular pressure. However, these drugs also produce a slight reduction in aqueous humor outflow through the trabecular meshwork whereby they could modify the effect of other drugs on intraocular pressure. As calcium channel blockers could be effective in the management of ocular hypertension and low-tension glaucoma, the aim of the present work was to assess the interaction between verapamil and timolol when both drugs are topically applied to the eye of albino rabbits. Intraocular pressure was measured with a manual applanation tonometer. The effects of 5-6 different doses of each drug alone and the effects of five mixtures of both drugs at fixed concentration ratios (timolol: verapamil 4:1, 2:1, 1:1, 1:2 and 1:4) were evaluated. After measuring baseline intraocular pressure, one 50 microliters drop of the different solutions was instilled in the left eye. Measures of the intraocular pressure were repeated at intervals of 30 min until the maximal effect was reached. Each set of experiments was carried out in a group of 9-11 rabbits. Dose-response curves were fitted with a nonlinear regression microcomputer programme. The median effect plot was constructed as proposed by Chou and Talalay (1981, 1983, 1984). In order to analyse the nature of the interaction between both drugs, the observed effect was compared with the theoretically expected one and the combination indices, that relate the doses of verapamil and timolol present in the mixtures with the doses of both drugs separately which are equieffective with the combination, were calculated. The effects of verapamil and timolol followed the principle of the mass action law when administered alone. Nevertheless, no adequate dose-response relationship was obtained when the mixtures of both drugs were applied. In general, the observed effects were lower than the expected ones. Combination indices also indicate the presence of antagonism, except for the lowest concentrations of mixtures where verapamil predominates. In this case, combination indices suggest summation of effects or synergy. Both drugs seem to decrease intraocular pressure by reducing aqueous humor secretion through different mechanisms. However, due to the reduction of aqueous humor outflow caused by verapamil, the ocular hypotensive effect of timolol may be antagonized when high doses of verapamil are administered.

Administration, Topical↗
PubMed1991

Argon-laser gonioplasty following goniosynechialysis.

We performed laser gonioplasty following goniosynechialysis on 12 eyes that exhibited a very narrow angle. In these cases, angle closure had recurred postoperatively, although gonioscopy carried out at the time of goniosynechialysis revealed opening of the trabecular meshwork. The use of laser gonioplasty following goniosynechialysis was most effective in flattening the configuration of the iris and opening the iridocorneal angle. The induced alteration of the structure of the iris remained unchanged in all cases throughout the follow-up period, and intraocular pressure remained below 20 mmHg in 9 of the 12 eyes. It thus appears that a combination of goniosynechialysis and laser gonioplasty may be effective in the management of refractory angle-closure glaucoma in the presence of an extremely narrow angle.

Acute Disease↗
PubMedDate not supplied

Glaucoma after vitreo-retinal surgery with silicone oil injection: epidemiologic aspects.

PURPOSE: To evaluate the prevalence of glaucoma after pars plana vitrectomy with silicone oil injection and to determine the different clinical forms. METHODS: Authors have carried out a retrospective longitudinal study on patients who underwent pars plana vitrectomy with silicone oil injection from 1981 to 1995. The examined population consists of 301 patients (301 eyes), with an age ranging from 8 to 85 years, affected by retinal detachment and proliferative vitreoretinopathy. RESULTS: The prevalence of the secondary glaucoma has been 18.5%. In all cases glaucoma was caused by trabecular meshwork obstruction due to silicone oil emulsification. The glaucoma has been more frequent after surgery for recurrent rhegmatogenous retinal detachment with fibrous PVR (52.86%) and for particular forms of rhegmatogenous retinal detachment (giant tears, multiple breaks, pseudophakia) with incipient PVR (30%). CONCLUSION: Glaucoma after intravitreal silicone oil injection for complicated retinal detachments is a relatively frequent complication mostly when surgery needs endophotocoagulation, endodiatermy and lensectomy.

Adolescent↗
PubMed1987

Immunohistochemical study of atrial natriuretic polypeptides in the embryonic, fetal and neonatal rat heart.

An immunohistochemical study of atrial natriuretic polypeptides was carried out on embryonic, fetal and neonatal rat hearts, using an antiserum raised against alpha-human atrial natriuretic polypeptide (alpha-hANP). Weakly immunoreactive cells were seen in both atrial and ventricular walls at 11 days post coitum (pc). After this stage, the immunoreactive cells became more intensely stained in both atrial and ventricular walls. The immunoreactivity during the prenatal period was stronger in the superficial cell layer beneath the endocardium, than in the deep cell layer of the atrial wall. The cells in the trabecular meshwork also had an apparent, but weak, immunoreactivity, which showed a greater intensity in the left ventricle than in the right one. It is suggested that these immunoreactive cells in the ventricle may differentiate, in situ, into the cells of the impulse-conducting system during the further development of the heart.

Animals↗
PubMed1982

The normal anatomy of the pig tailed macaque (Macaca nemestrina) outflow apparatus with particular reference to the presence of smooth muscle.

The normal anatomy of the pig tailed macaque (Macaca nemestrina) outflow system has until now been undocumented. Tissue from ten monkeys was investigated by light microscopy, transmission electron microscopy and scanning electron microscopy. Although the basic configuration of the outflow apparatus was similar to other subhuman primates it did differ in the following aspects: a) bundles of circumferentially orientated smooth muscle cells were present in the outer and posterior part of the trabecular meshwork near Schlemm's Canal, b) large 'atypical' endothelial cells with microfilament rich cytoplasm were present in the cribriform layer, c) numerous collagenous cords and septae were present in Schlemm's Canal which also appeared to be drained by more than the usual number of collector channels. The possible importance of these anatomical differences is discussed.

Animals↗
PubMed1983

Carbonic anhydrase distribution in the human and monkey eye by light and electron microscopy.

The distribution of carbonic anhydrase (CA) in the eye of man and three species of monkeys was studied by light and electron microscopy using the histochemical method of Hansson. Carbonic anhydrase staining was found in the corneal endothelium. In monkeys the endothelial cells covering the inner surface of the operculum were also stained, whereas in the human the staining stopped at Schwalbe's line. In the trabecular meshwork no cells exhibited CA staining. The iris dilator muscle showed some staining, while no clear staining was found in the pigment epithelium (PE). In the ciliary body both the PE and the non-pigmented epithelium (NPE) displayed CA staining, most prominently in the basal and lateral membranes but also discernible in the cytoplasm. The staining of the NPE (but not the PE) showed clear-cut regional differences, and the presence of CA coincided with morphological indicators of secretory activity. Heavy staining was found in the capillaries under the ciliary epithelium. In the pars plana many capillaries showed staining of only that part of the circumference of the vessel wall which faced the epithelium. Unstained segments were also found in many choroidal capillaries under the pigmented epithelium of the retina. In the retina itself CA stain was found in the pigmented epithelium, in the Müller cells and in capillaries supplying the inner retina (only monkey retina was studied).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Type-VI collagen in the human iris and ciliary body.

The distribution of type-VI collagen in the human iris and ciliary body was investigated by means of immunohistochemical techniques and compared with that of type-IV collagen, fibronectin and laminin. As has been described for other tissues, type-VI collagen surrounds type-I and -III collagen fibers. The aggregated form of type-VI collagen (the "long-spacing" or "curly" collagen), which has already been described in the trabecular meshwork and sclera, was also observed at the ciliary muscle tips surrounding the anterior elastic tendons of this muscle. In addition, staining for type-VI collagen was seen directly adjacent to the basement membranes of the ciliary muscle cells, the iris muscles, the uveal vascular endothelia and nerves, but not adjacent to the epithelial basement membranes. The staining did not form a discrete line like the immunoreaction for type-IV collagen, but bundles of marked fibrils extended into the surrounding connective tissue. We assume that type-VI collagen similar to type-VII collagen forms part of an anchoring system for these tissues. As type-VII collagen has been described only in connection with epithelial basement membranes, both type-VI and type-VII collagens may represent anchoring fibrils, however for different tissue components.

Aged↗
PubMed1975

Corneal superficial unwettable defect. II. Electron microscopic study.

Corneal biopsy specimens of 6 patients with this particular affection were studies with the electron microscope. In addition to the routine electron microscopic methods, staining with ruthenium red was performed on one excised specimen. Marked changes were found in the region of Bowman's membrane, which was altered either superficially or in its total width. Its collagen fibrils became rough and intensively electron-dense, forming a granular or structureless trabecular meshwork. Intertrabecular spaces were filled with special electron-lucent material, which also formed a continuous layer on the surface of the altered Bowman's membrane. Filamentous structures resembling fingerprints were observed in certain areas of these spaces; and after staining with ruthenium red, numerob granules were also visible. Both these structures are considered by the author to be acid mucopolysaccharides. There is further discussed on the correlation of these findings with previous histochemical findings; the author gives special attention to the question whether waxy substances-eye ointment bases-could have been deposited in the pathologically altered Bowman's membrane.

Biopsy↗
PubMed1976

Glucocorticoids and intraocular pressure: an experimental study.

The state of intraocular pressure and aqueous humor dynamics as well as histomorphologic and histochemical change of the eye tissues as a result of administration of glucocorticoids were studied in 62 rabbits. After administration of glucocorticoids by instillations and subconjunctival injections there was a trend toward increased intraocular pressure but no statistically significant change in the intraocular pressure was demonstrated. When glucocorticoids were administered for 1 month, a significant increase in production and outflow of aqueous humor was established. Continuation of the experiments for 2 months or longer was accompanied by a significant decrease of the outflow facility coefficient and inhibition of aqueous humor formation. Histologic and histochemical examinations of the eyes of the rabbits studied for 2 months revealed marked dystrophic changes in the trabecular meshwork tissues.

Animals↗
PubMed1997

Ocular involvement in familial erythrophagocytic lymphohistiocytosis.

BACKGROUND: Familial erythrophagocytic lymphohistiocytosis (FEL), a rare, rapidly fatal childhood disorder, is characterized by intermittent fevers, hepatosplenomegaly, cytopenia, hypercytokinemia and lymphohistiocytic infiltration with erythrophagocytosis involving multiple organs. We report the clinical and histological features of two infants with FEL and emphasize the ocular findings. METHODS: Microscopic examination of formalin-fixed, paraffin-embedded autopsy material was performed. Immunohistochemical studies were performed in case 1. RESULTS: The first patient presented with clinical and laboratory features and a family history consistent with FEL, and a liver biopsy revealed a lymphohistiocytic infiltrate with erythrophagocytosis consistent with FEL. A deceased brother had been diagnosed with FEL. Autopsy showed widely disseminated lymphohistiocytic infiltrates affecting the liver, spleen, bone marrow, lungs, kidneys and brain. Histologic examination of both eyes disclosed a prominent lymphohistiocytic infiltrate of the optic nerve with destruction of nerve fiber bundles as well as milder infiltrates in the choroid, scleral canals, perineural areas in the orbit and the optic nerve head perivascularly. The second patient also had the typical clinical, laboratory and autopsy findings with similar involvement of most organs, including extensive infiltration of the spleen and bone marrow. Histologic examination of one eye revealed marked lymphohistiocytic infiltration of the entire choroid as well as milder infiltration in the trabecular meshwork, iris, ciliary body, optic nerve, meninges and around the central retinal vein in the optic nerve. CONCLUSION: The findings of this study further define the ocular pathologic features of FEL, which are a part of a generalized, multiorgan disseminated disease.

Choroid↗
PubMed1978

Degeneration and regeneration of autonomic nerve endings in the anterior part of rhesus monkey ciliary muscle.

The autonomic nerve plexus of the ciliary muscle was examined with the electron microscope in normal rhesus monkeys of different ages. In the anterior region of the muscle, at the boundary with the poorly innervated scleral spur and trabecular meshwork, 3.8-7.1% of the axons exhibit either degenerative or regenerative features. The cytoplasm of degenerating axons contains lamellated, dense and multivesicular bodies, vesicles, whorls of filaments, and membranous debris. The plasma membrane is often discontinuous and, on occasion, axonal debris and degenerative organelles are freely dispersed in the connective tissue spaces of the muscle. Degenerating axons contain a granular reaction product when stained for acid phosphatase activity. Regenerating axons are characterized by tightly packed mitochondria, glycogen particles, and aggregates of synaptic vesicles; they synapse with muscle cells and are negative to the acid phosphatase reaction. A quantitative analysis showed that in the anterior region of the ciliary muscle degenerating and regenerating axons increase in number with age, although the total number of axonal profiles remains constant. In the age groups examined, degenerating axons occurred with the same frequency as regenerating axons, thus, the age-dependent increase in axonal degeneration is accompanied by a parallel increase in axonal regeneration. We conclude that autonomic nerve endings in the anterior part of the ciliary muscle undergo a continuous process of renewal that is more prominent in old age.

Acid Phosphatase↗
PubMed1986

Histochemistry of elastic and related fibres in the human eye in health and disease.

Although the presence of mature elastic fibres in the sclera, trabecular meshwork and Bruch's membrane of the human eye has been recognized for many years, it is only latterly that the existence of the elastic-related fibres oxytalan and elaunin has been appreciated. The microfibrillar component of elastic, oxytalan, which is present in several ocular structures in infancy, can either mature to fully-developed elastic tissue or, as in the cornea, disappear in subsequent years. Deposition of elastic fibres, particularly the incomplete forms, can occur in the post-developmental period in a variety of disease states but the stimulus and functional significance in most situations is obscure. The evidence suggests, however, that the capacity to form elastic-related tissue is not confined to any one cell type.

Contractile Proteins↗
PubMed1985

Wedge-shaped retinal nerve fiber layer defects in experimental glaucoma preliminary report.

Many investigators have reported that abnormalities in the retinal nerve fiber layer may be the earliest sign of primary open-angle glaucoma. We attempted to create defects in the retinal nerve fiber layer in experimentally induced glaucoma and to examine their histology. By repeated circumferential argon laser photocoagulation of the trabecular meshwork of normal cynomolgus monkeys, we succeeded in causing a continuous increase in intraocular pressure (IOP). During the course of this experiment, cupping of the optic nerve head, wedge-shaped retinal nerve fiber layer defects, and halo glaucomatosus developed, all of which are defects that are similar to those seen clinically in primary open-angle glaucoma. The IOP required for this fundus change was 25, 35, and 43 mmHg, indicating great individual variation. Histological examination revealed localized degeneration, loss of axon bundles, and diffuse thinning of the nerve fiber layer in the area of these wedge-shaped defects in the retinal nerve fiber layer. These results may indicate that the optic-nerve-damaging mechanism, both localized and generalized, is the same in the cynomolgus monkey and in man.

Animals↗
PubMed2003

Beta 2-adrenergic receptor polymorphism and susceptibility to primary congenital and primary open angle glaucoma.

OBJECTIVE: It has been shown that arginine to glycine (Arg16Gly), glutamine to glutamic acid (Gln27Glu) and threonine to isoleucine (Thr164Ile) exchanges in codons 16, 27 and 164, respectively, of the beta 2-adrenergic receptor (B2AR) gene significantly alter receptor function. As B2ARs are located on the afferent blood vessels supplying the ciliary body and trabecular meshwork cells, which control aqueous humour dynamics, polymorphisms of B2AR may be involved in the pathophysiology of certain eye diseases, such as glaucoma. Therefore, the aim of the present study was to investigate the distribution of B2AR polymorphisms in patients with primary congenital and primary open angle glaucoma. METHODS: A group of 30 patients with primary congenital glaucoma, 105 with primary open angle glaucoma and 92 control patients were analysed for the Arg16Gly, Gln27Glu, and Thr164IIe polymorphisms of the B2AR by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The allelic frequencies of Gly16, Glu27 and IIe164 variant alleles were 66.7, 38.3 and 3.3% in patients with congenital glaucoma, 59.5, 31.0 and 1.0% with glaucoma, and 54.9, 26.6 and 0.5% in controls, respectively. Although statistically non-significant, the frequencies of variant alleles were slightly higher in both groups of the glaucoma patients. CONCLUSIONS: These results suggest no evidence of an association between the Arg16Gly, Glu27Gln and Thr164Ile polymorphisms of the B2AR gene and risk of developing primary open angle glaucoma or primary congenital glaucoma. However, further studies are needed to understand the role of B2AR polymorphisms in patients with eye disease.

Child↗
PubMed2000

[Intraocular pressure reduction by endoscopically controlled erbium:YAG goniotomy].

BACKGROUND: Microperforations of the trabecular meshwork can be made using an endoscope guided Er:YAG laser. As shown in enucleated human melanoma eyes, these microperforations are not accompanied by thermal damage of the surrounding tissue. We now report our first clinical results using a commercially available endoscope/laser system for performing this particular kind of goniotomy. PATIENTS AND METHOD: A combined cataract extraction and Er:YAG goniotomy was performed in 24 eyes of 20 patients. Seventeen eyes were reexamined after a minimum follow-up of 4 months (mean 6.5 months, max. 12 months). The results were compared to a control group having only the cataract operation (14 eyes). RESULTS: After combined cataract operation and Er:YAG goniotomy, mean intraocular pressure dropped from 21.8 to 15.5 mmHg. Intraocular pressure regulation was successful in 88% of these cases. In contrast to this, the intraocular pressure reduction in eyes having only the cataract operation was much less pronounced (mean intraocular pressure preoperative 20.0, postoperative 17.4, success rate 35%). CONCLUSION: The first results with our particular endoscope/laser system are encouraging. Other groups using comparable devices have reported similar success rates. We hope that the endoscopic Er:YAG goniotomy may become a minimally invasive type of glaucoma surgery in the near future.

Aged↗