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Balloon cell melanomas of the ciliary body.

In spite of the fact that balloon cell change has been recognized ophthalmoscopically and histologically in certain posterior choroidal melanomas, the nature and importance of this observation remain controversial. This article provides a clinicopathologic correlation in two cases of ciliary body melanoma with almost total balloon cell transformation. On the basis of special stains and electron microscopic observations, we have concluded that balloon cells in such cases represent spindle melanoma cells that have undergoing extensive cytoplasmic lipid metamorphosis. The possible mechanisms for this change are considered. Melanomas containing an abundant number of balloon cells are probably comparatively dormant and benign tumors that offer a relatively good prognosis. Although clinical recognition may be difficult, the use of needle biopsy coupled with cytologic diagnosis in selected ciliary body tumors may disclose balloon cell change and help to direct therapy.

Cataract↗

[Morphometric analysis of age-dependent changes of the human ciliary body].

Morphometric and stereologic techniques have been applied to human ciliary epithelium and bordering stroma of 31 (respectively 16) normal donor eyes aged 15 to 86, providing quantitative information on the age-related structural changes of ciliary body tissue. Aging appeared to result in a generalized widening of the stromal layer from 19.3 +/- 2.4 microns (10-20 years; n = 4) to 60.0 +/- 11.5 microns (80-90 years; n = 3) in ciliary processes and from 53.0 +/- 6.8 microns to 107.6 +/- 15.2 microns in the ground plate between ciliary valleys and ciliary muscle, a density increase of collagenous fibers from 39.3 +/- 4.9 to 83.5 +/- 14.6 fibers/microns 2 and a concomitant decrease in mean fiber diameter from 62.8 +/- 3.4 nm to 55.7 +/- 1.5 nm, a decline of stromal cell density from 31.4 +/- 1.8 to 9.6 +/- 1.0 cells/0.014 mm2, a progressive thickening of the inner and outer limiting membranes from 0.8 +/- 0.4 micron to 8.1 +/- 1.5 microns and 2.1 +/- 0.6 microns to 4.5 +/- 0.5 microns respectively as well as the endothelial basement membrane from 0.13 +/- 0.004 micron to 0.25 +/- 0.03 micron, a gradual widening of the perivascular space between capillaries and overlying pigment epithelium from 6.2 +/- 1.5 microns to 11.3 +/- 2.9 microns, an increase in number of fenestrations in the capillary endothelium from 39.0 +/- 8.5 to 69.0 +/- 7.0 pores/100 microns, and finally a continuous augmentation of degenerative elements including lipids, lipofuscin granules, and lysosomes from 1.5 +/- 0.06% to 7.2 +/- 0.6% within the non-pigmented epithelium (NPE) over the 71-year period studied. Regression analysis yielded a highly significant impact of age on these morphometric parameters, while the relative volumes of the remaining cell compartments of the NPE-cells revealed no statistically significant correlation with age. Rather, the variations in volume densities of Golgi bodies (0.34 +/- 0.25%; n = 16) and pigment granules (0.36 +/- 0.27%; n = 16) seemed to be random with respect to age, whereas the relative volumes of mitochondria (21.7 +/- 1.8%; n = 16) and RER (5.9 +/- 0.7%; n = 16) remained fairly constant indicating that the NPE-cells maintain their functional capacity with advancing age. Age-related reduction of aqueous humor formation therefore appears to be rather due to impaired fluid passage from vasculature to ciliary epithelium than to functional incompetency of the NPE.

Adolescent↗

Hyperglycemia in streptozotocin-induced diabetes leads to persistent inflammation and tissue damage following uveitis due to reduced levels of ciliary body heme oxygenase-1.

This study investigated the heme oxygenase-1 (HO-1) and the endotoxin-induced uveitis (EIU) in diabetic streptozotocin (STZ)-hyperglycemic rats. STZ-hyperglycemic rats had impaired levels of the enzyme HO-1 within the ciliary bodies if compared with the nondiabetic rats. STZ-hyperglycemic rats also predisposed the eye to produce high levels of both the cytokines IL-1beta and CXCL8. Subsequent EIU further and significantly (P < .01) increased the cytokines production, an effect partly prevented by hemin treatment. Most importantly, hemin, an inducer of heme oxygenase expression and activity, recovered the huge number of infiltrated polymorphonuclear leukocytes PMN within the ciliary bodies associated with STZ-hyperglycemic state and EIU damage. Impairment of the stress-sensitive enzyme HO-1 in STZ-hyperglycemic rats increases and prolongs the inflammatory response to EIU.

Animals↗

Laminin subtype distribution in the human ciliary body.

PURPOSE: Laminin is a family of heterotrimeric molecules each consisting of a heavy chain (A or M chain), and two light chains (B1, B2, or S chains). In this study the distribution of these chains was determined in human ciliary body. METHOD: Tissue slices from five postmortem eyes were incubated with monoclonal antibodies against the chains and with a fluorescent secondary antibody. After the tissues were embedded in Spurr's resin, 1-micron thick sections were obtained. RESULTS: Uniform staining with A, S, and B2 laminin chains was observed in basement membrane surrounding muscle bundles. Inside the bundles, the basement membrane around individual fibers was evenly stained by S and B2; however, only some fibers had A-chain immunoreactivity. The basement membrane of blood vessels was also stained with A, S, and B2. Stromal connective tissue was not stained. Ciliary pigmented epithelium basement membrane demonstrated A, S, and B2 immunoreactivity, but not B1 immunoreactivity. Adjacent to the nerves, M, S, B1, and B2 immunoreactivity was detected. CONCLUSION: The results indicate that A-S-B2 laminin is present in the basement membranes associated with smooth muscle bundles, blood vessels, and the nonpigmented and pigmented epithelia. A-B1-B2 laminin is also found in the pigmented epithelium basement membrane. M-B1-B2 and M-S-B2 are found in association with nerve tissue. This heterogeneity in the basement membranes of the ciliary body suggests that they mediate different cellular functions.

Adult↗

Mifepristone blocks specific glucocorticoid receptor binding in rabbit iris-ciliary body.

Mifepristone is a specific glucocorticoid receptor antagonist that has been shown to lower intraocular pressure modestly when applied topically to rabbit eyes. We evaluated the ability of mifepristone to block specific in vitro glucocorticoid receptor binding of the labeled agonist triamcinolone acetonide in cytosol isolated from rabbit iris-ciliary body tissue. A 500-fold molar excess of nonradioactive mifepristone completely blocked specific binding of triamcinolone acetonide to glucocorticoid receptors in the iris-ciliary body cytosol. Additionally, specific binding was blocked in a dose-dependent fashion over a range of 0.005-fold to 500-fold molar excess of mifepristone. Mifepristone's effect on intraocular pressure may be due to its ability to antagonize glucocorticoid receptor-mediated effects in ocular tissues.

Animals↗

The zonules and the elastic microfibrillar system in the ciliary body.

It has been proposed that elastic fibers occur in some tissues as a three-part interconnecting system. The system includes two sizes of elastin-containing fibers surrounded by tubular microfibrils (elastic microfibrils), besides isolated bundles of tubular microfibrils without elastin (oxytalan fibers). This little-studied system was identified in the bovine ciliary body by light and electron microscopy. Its architecture varied regionally, suggesting different vectors of tractional force in the anterior and posterior ciliary body related to accommodation. Zonular fibers had the staining characteristics of oxytalan fibers, and their fibrils were ultrastructurally similar to the tubular microfibrils around elastic fibers and those composing oxytalan fibers. Antibodies to microfibrillar protein bound to zonules and to tubular microfibrils in all sites. This is the first evidence that tubular microfibrils both with and without elastin share antigenic determinants and confirms the close antigenic relationship of the zonules to this class of proteins.

Animals↗

Nucleolar diameter and microvascular factors as independent predictors of mortality from malignant melanoma of the choroid and ciliary body.

PURPOSE: To determine whether nucleolar diameter and microvascular factors are independent predictors of mortality in malignant uveal melanoma of the choroid and ciliary body. METHOD: A population-based retrospective cohort study was conducted of melanoma-specific and all-cause mortality in 167 consecutive patients who had an eye enucleated because of choroidal and ciliary body melanoma from 1972 through 1981. The largest nucleoli were measured from digital photographs of silver-stained tumors along a central 5-mm-wide linear field parallel to the base of the tumor. The mean of the 10 largest nucleoli (MLN) was calculated. Microvascular loops and networks and microvascular density (MVD) were assessed. Kaplan-Meier and Cox regression analyses were performed. Associations between MLN and other variables were determined. RESULTS: The MLN could be determined in 126 (75%) melanomas. It ranged from 2.60 to 6.18 microm (median, 4.05). The association of large MLN with the presence of epithelioid cells (P = 0.017) and high MVD (P = 0.0053) was statistically significant. MLN was not significantly associated with tumor diameter and microvascular loops and networks. The 10-year melanoma-specific survival decreased with MLN (0.74, 0.60, and 0.42, arranged in tertiles; P = 0.0060), presence of loops and networks (P = 0.0001), and increasing MVD (P = 0.0001). By Cox regression, MLN was an independent predictor of survival, when adjusting in turn for presence of epithelioid cells, loops and networks, and MVD. In multivariate models with MVD, the independent prognostic information carried by MLN decreased, but the model as a whole was a better predictor of survival. The magnitude of this effect depended on whether MLN was modeled as a continuous or categorical variable. CONCLUSIONS: In this population-based data set, MLN and microvascular loops and networks were unrelated, independent predictors of survival. MLN and MVD were found to be partially interrelated. Multivariate models that included MVD in addition to MLN fitted better with observed melanoma-specific survival than models that excluded MVD.

Antigens, CD34↗

The effect of transscleral laser cyclophotocoagulation on rabbit ciliary body vascularization.

Long-term changes in the vascular network of rabbit ciliary processes induced by Nd:YAG laser cyclophotocoagulation were examined both from a morphological viewpoint and with respect to three-dimensional organization (in vascular casts). Relative changes in intraocular pressure (IOP), monitored within eyes irradiated across one-quarter, one-half, three-quarters, or all of the ciliary body circumference, are discussed in relation to morphological changes. The clinical implications of these findings are considered.

Animals↗

[Surgical method for the treatment of irreversible angle-closure glaucoma and aphakic glaucoma. Direct ciliary body coagulation with partial cyclodialysis].

Among 16 patients aged from 31 to 86 there were 13 cases of hemorrhagic glaucoma, three cases of secondary glaucoma from iritis and one case of secondary angle-closure glaucoma after trauma. Reduction in intraocular pressure was achieved by a surgical method which primarily aims to improve the outflow of aqueous humor. The ciliary body is laid bare by preparation of a scleral flap, a partial cyclodialysis is attached on both sides and the ciliary body is induced to stricture by coagulation, so that a large enough cleft is created. Before the operation, pressure ranged from 34 to 64 mm Hg; after the operation, during postoperative periods of observation lasting from two to 32 months, there were 14 cases in which the pressure was below 25 mm Hg and two cases with 30-40 mm Hg respectively. In view of the good results and the few complications, this method of operation can be recommended for treatment of both irreversible angle-closure glaucoma and aphakic glaucoma.

Adult↗

Binding of timolol to iris-ciliary body and melanin: an in vitro model for assessing the kinetics and efficacy of long-acting antiglaucoma drugs.

Topical beta blockers are used to treat glaucoma patients. These drugs inhibit aqueous production for prolonged periods of time. The purpose of this study was to determine whether timolol maleate (a non-specific beta blocker) binds to human iris-ciliary body (CB) melanin and to elucidate the binding characteristics of the drug to melanin. Timolol bound to bovine iris and ciliary body by two possible mechanisms. The binding kinetics indicate that the binding is probably of a nonspecific nature. There was no statistically significant differences between the melanotic tissues (CB, iris) and the nonmelanotic tissues (lens, cornea, liver, kidney) regarding the amount of timolol bound. However significantly more timolol was bound to the isolated melanins than the whole tissues. Timolol was released from the nonmelanotic tissues at a much faster rate than from the melanotic tissues. The amount of timolol bound to iris-CB from albino and pigmented rabbits showed that the amount of timolol bound to these tissues diminished in the following order: black or gray greater than brown greater than albino. It was also found that the rate of timolol release decreased in the following order: albino greater than gray greater than brown or black. Our results demonstrate the binding of beta blocker to human, bovine and rabbit iris-CB and consequent slow release of timolol from these tissues.

Adrenergic beta-Antagonists↗

Delta-opioid agonist-stimulated inositol phosphate formation in isolated, rabbit iris-ciliary bodies: role of G(i/o) proteins and Gbetagamma-subunits.

Our laboratory has previously demonstrated the ability of kappa- and delta-opioid agonists to decrease aqueous flow rates and intraocular pressure of rabbits. The mechanisms by which these agents act in the ciliary body of the rabbit could involve inhibition of cAMP production, as well as increased generation of inositol phosphates (IPs). With regard to enhanced production of IPs, it has been suggested that their levels can be augmented by stimulation of phospholipase C via opioid receptors linked to either Galpha-subunits derived from Gq proteins or Gbetagamma-subunits derived from G(i/o)-proteins. The aim of the current study is to investigate the role of pertussis toxin (PTX)-sensitive G-proteins and Gbetagamma-subunits in delta-opioid agonist-mediated changes in IP production in the isolated, rabbit iris-ciliary body (ICB). In one set of experiments, ICB segments were treated with the delta agonist, SNC80 (10(-12)-10(-7) mol/l) alone. Other experiments were conducted utilizing SNC80 following pretreatment with either phosducin (Gbetagamma-subunit scavenger), PTX, or the delta antagonist, naltrindole. IP production was measured by ion exchange chromatography. Basal levels of IPs in the rabbit ICB were 58,287 +/- 2162, 15,218 +/- 969 and 2083 +/- 367 dpm/mg protein for IP1, IP2 and IP3, respectively. The highly selective delta-opioid receptor agonist, SNC80, produced concentration-dependent increases in the levels of the IPs in the ICB, which were diminished in the presence of the delta antagonist, naltrindole, indicating the effect was mediated via activation of delta-opioid receptors. Pretreatment of tissues with PTX (75 ng/ml), completely abolished the concentration-dependent production of IPs generated by SNC80 (10(-11)-10(-7) mol/l). In addition, pretreatment with phosducin (1 nmol/l) ablated the SNC80 (1 nmol/l)-induced increase in the formation of all three inositol phosphates. Results from this study indicate that the delta-opioid receptor-mediated increase in IP production is a PTX-sensitive G(i/o) response that involves participation of Gbetagamma-subunits. Thus, delta-opioid receptor activation by SNC80 in the ICB could be responsible, in part, for suppression of aqueous humor dynamics.

Animals↗

Sulfated glycolipids in ciliary body epithelium.

The sulfated material which locates in the basal membrane of ciliary body epithelium when immature rat eyes are incubated with Na235SO4 was studied. On the basis of its chromatographic behavior compared with standard preparations, we conclude that the material consists of sulfatides.

Animals↗

Ciliary body melanoma with optic nerve invasion.

A case of melanoma of the ciliary body is presented. Initially the patient was diagnosed and treated for uveitis, but following CT scanning and ultrasound a tumour was detected and the eye enucleated. Histopathologically it was found that the tumour had invaded the optic nerve head, apparently via Cloquet's canal.

Adult↗

An atypical vasopermeability response to leukotrienes in the iris-ciliary body.

The effects of leukotrienes (LTs) on the blood-aqueous barrier in the guinea pig were investigated. Leukotriene B4 (LTB4) and D4 (LTD4) were administered in doses of 1 to 1000 ng into the anterior chamber. Plasma extravasation was determined as extravascular 125I-albumin levels in the iris-ciliary body using 125I-albumin and 51Cr-erythrocytes as an intravascular marker. LTB4 and LTD4 alone did not cause significant plasma extravasation. Although combinations of 100 ng and more of each LT raised extravascular albumin levels in the ocular anterior uvea. These studies suggest a synergistic interaction of LTB4 and LTD4 with respect to plasma extravasation in the iris-ciliary body. These results further support a possible involvement of LTs in uveal inflammatory diseases.

Animals↗

Sodium and chloride transport across the isolated rabbit ciliary body.

Unidirectional Na+ and Cl- fluxes were determined in the isolated rabbit ciliary body under short-circuited conditions. A statistically significant net Cl- flux towards aqueous was detected in the standard bathing solution (HCO3- = 115 mM), but no net Na+ flux was demonstrated in this solution. The net Cl- flux exceeded the short-circuit current, suggesting the existence of a net flux of other ion(s). In a bathing solution containing 5 mM HCO3-, the net Cl- flux was abolished, suggesting that HCO3- in the bathing solution enhances the net Cl- flux.

Action Potentials↗