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Localization of organic anion transporting polypeptides in the rat and human ciliary body epithelium.

PURPOSE: To identify and localize the expression of multispecific organic anion transporting polypeptides (Oatps/OATPs) in the ciliary body epithelium and to investigate their possible involvement in the transport of the antiglaucoma agent unoprostone. METHODS: Oatps/OATPs were detected by immunoblot analysis and by immunofluorescence microscopy in homogenized and fixed rat and human ciliary body samples using specific polyclonal antibodies. Transport of 3H-labelled unoprostone was measured in Oatp/OATP expressing Xenopus laevis oocytes. RESULTS: Immunoblots of ciliary body extracts were positive for rat Oatp1a4, Oatp1a5 and Oatp1b2 and for human OATP1A2, OATP1C1, OATP2B1, OATP3A1 and OATP4A1. Confocal immunofluorescence microscopy localized Oatp1a4 and Oatp1b2 as well as all immunoblot positive human OATPs at the basolateral plasma membrane of the non-pigmented rat and human ciliary body epithelium, respectively. However, for human OATPs additional regional differences in expression were found with OATP1A2 and OATP1C1 being expressed only in the pars plana of human ciliary body epithelium. Furthermore, OATP1C1, OATP3A1 and OATP4A1 were also expressed at the basolateral plasma membrane of the pars plana pigmented epithelium. And finally, deesterified unoprostone carboxylate was found to be transported by OATP1A2, OATP2B1 and OATP4A1 with approximate K(m)-values of 93, 91 and 132 microm, respectively. CONCLUSIONS: Several multispecific organic anion transporting polypeptides are expressed at the basolateral plasma membrane of the non-pigmented, and to a lesser extent also of the pigmented, epithelium in rat and human ciliary body. These Oatps/OATPs can account for the previously suggested 'liver-like' transport functions of mammalian ciliary body epithelium.

Adult↗

The heredity and treatment of angle-closure glaucoma secondary to iris and ciliary body cysts.

Three families with peripheral iris and ciliary body cysts are described. The cysts were multiple in 10 of the 11 affected patients, and they were bilateral in 8 of the 11. Angle closure glaucoma secondary to the cysts was present in 4 of the 11 cases. The management of this glaucoma requires a high index of suspicion, careful gonioscopic evaluation and proper medical and/or surgical treatment. Laser therapy for the angle closure caused by pigmented cysts may be curative. Nonpigmented ciliary body cysts are refractory to argon laser treatment and carry a poor prognosis. The cases described suggest an autosomal dominant hereditary pattern. The importance of examination and follow up of healthy relatives of patients with iris and ciliary body cysts is stressed, as early detection and treatment by laser cystotomy may prevent or cure angle closure glaucoma if the disease is diagnosed prior to the establishment of synechial closure.

Adult↗

Ciliary body schwannoma successfully treated by local resection.

BACKGROUND: Schwannoma arising from the ciliary body is a rare intraocular neoplasm, and most cases previously reported were diagnosed histopathologically after eyeball enucleation because of a diagnosis of ciliary body melanoma. CASE: A case of ciliary body schwannoma was dissected locally. OBSERVATIONS: A 19-year-old woman was referred to us with a diagnosis of iris cyst. Local resection of the tumor was performed because of deteriorated visual acuity caused by displacement of the lens. In histopathological analysis, the encapsulated tumor showed a proliferation of the spindle cells with no atypia, and in immunohistochemical analysis, tumor cells were positive for S-100 protein; these findings were compatible with schwannoma. Visual acuity improved postoperatively, and no complications or recurrence have been observed in the 4 years since surgery. CONCLUSIONS: Schwannoma should be considered in the differential diagnosis of a ciliary body tumor.

Adult↗

[Acetylcholine in the bovine ciliary body and the cholinergic action of pilocarpine].

The authors have determined the acetylcholine (ACh) content in bovine ciliary bodies. One of the ciliary bodies was subjected in vivo to the influence of an aqueous solution of pilocarpine HCl 3 p. 100 which was instilled in the conjunctival cul-de-sac (ten times at a dose of three drops every three minutes). The contralateral ciliary body of the same animal served as a control for the ACh concentration. Enucleation was performed one hour after the last instillation. The average concentration of ACh estimated in 13 control ciliary bodies was 0,40 mug of ACh, and in 13 pilocarpinised eyes 0,50 mug of ACh (for 150 mg of tissue). The questions concerning the inactivation of pilocarpine and the source of augmentation of cholinergic tone in the pilocarpinised eyes have been discussed in previous communications.

Acetylcholine↗

[Clinical analysis of tumors of the iris and ciliary body].

OBJECTIVE: To evaluate the clinical features, different diagnosis, pathological features, management, and prognosis of tumors of the iris and ciliary body. METHODS: Medical records, photographs, pathological findings and the results of follow-up of 37 cases with tumors of the iris and ciliary body were reviewed as a retrospective study. RESULTS: Of the 37 cases with tumors of the iris and ciliary body, 26 were male and 11 were female. The mean age at diagnosis was 38 years, ranged from 5 - 64 years. According to the histopathological examination, melanoma was the most common tumor in the iris and ciliary body (15 cases, 40.5%), followed by metastatic tumors (8 cases, 21.6%), teratoid medulloepitheliomas (3 cases, 8.1%) and iris nevus (2 cases, 5.4%). MANAGEMENT: The tumors were excised in 14 cases. Enucleation was performed in 21 cases. Two cases were observed without any surgical treatment. Thirty-four cases were followed-up for 2 months to 15 years, averaged 31 months. Most melanomas of the iris and ciliary body are round or semi-spherical dark brown vascularized mass, with engorged episcleral sentinel vessels in some cases. The tumor showed a shadow during transillumination. Ultrasound biomicroscopy revealed a low to medium echoic solid lesion, with echoic changes in adjacent infiltrated tissues. Melanoma showed positive immunoreactivity for melanoma-specific antigen, and had a good prognosis. Metastatic tumors of the iris and ciliary body were flat or near round, dirty, single or multiple neoplasms, growth rapidly, with abundant neovascularization, and had a poor prognosis. Primary carcinomas could be found in other parts of the body. CONCLUSIONS: Melanoma of the iris and ciliary body has typical features that may help to distinguish them from other tumors. Metastatic tumor has characteristic features, but the diagnosis can be made only with supplementary examination and immunocytochemical studies. Medulloepitheliomas should be differentiated from retinoblastoma.

Adolescent↗

Expression and distribution of matrix metalloproteinases and their inhibitors in the human iris and ciliary body.

AIM: To determine the expression and distribution of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in the normal human iris and ciliary body. METHODS: Seven postmortem human eyes were fixed with formalin. The iris and ciliary body were dissected out and embedded in paraffin. The expression of MMPs -1, 2, 3, and 9, and TIMPs 1-4 in the iris and ciliary body was determined by a novel immunofluorescence technique and the results graded by masked observers. RESULTS: Positive staining for MMPs and TIMPs was observed in all regions of the anterior uvea, and was more intense in the ciliary body than in the iris. Most MMPs and TIMPs showed similar patterns in their distribution. In the ciliary body, staining was strongest in the epithelium, and was localised to the epithelial cell cytoplasm, except for TIMP-3 which was strongly expressed in the basement membranes. In the iris, staining was most noticeable in the anterior border and anterior epithelial layer. Blood vessels in the stroma of the iris and ciliary body also stained moderately for MMPs and TIMPs. CONCLUSION: Both MMPs and TIMPs are widely expressed in the anterior uvea, with a positive correlation between their expressions. Their differential localisation in the ciliary body suggests they may have a role in maintaining homeostasis in the uveal tract.

Aged↗

Corneal edema with a ciliary body melanoma.

A 40-year-old woman is described with a ciliary body melanoma presenting with localized corneal edema and keratic precipitates. A ciliary body mass was visualized when the pupil was dilated. The mass was excised by corneoscleroiridocyclectomy and was a spindle B melanoma of the ciliary body. There has been no evidence of recurrence of the tumor, and the visual acuity has been stable at 20/25 for the past 3 years. This is the first case known to us of a ciliary body melanoma presenting with localized corneal edema and keratic precipitates.

Adult↗

Spontaneous fluid transport across isolated rabbit and bovine ciliary body preparations.

PURPOSE: To quantify spontaneous fluid transport across the isolated ciliary bodies of rabbit and bovine and to determine their osmotic permeabilities. METHODS: A complete annulus of ciliary body was mounted in a custom-designed chamber appropriate for detecting net fluid movement across the in vitro preparation. RESULTS: A net fluid flow in the blood-to-aqueous direction was measured. It was generally observed that tissue freshness is a critical parameter for detection of such flow. The spontaneous, baseline fluid transport rate lasted, on average, approximately 4 hours. This flow solely reflects the secretory activity of the isolated ciliary epithelium, since the in vitro arrangement precludes contributions from ultrafiltration. Both the isolated rabbit and bovine ciliary body epithelia transported fluid in the absence of an external osmotic or pressure gradient. After corrections for area and possible collapse of the processes, a total flux rate of approximately 23 microL/hour or 13% of the in vivo flow in rabbit was estimated. This value agrees with predictions of ionic fluxes and short-circuit current measurements, which are also obtained in vitro. The fluid flow is bicarbonate dependent in rabbit and chloride dependent in bovine, consistent with ionic transport mechanisms described in these species. Ouabain inhibited the fluid flow across both species, indicating dependence on active ionic transport. Irrespective of the spontaneous fluid transport, a flow elicited by an osmotic gradient allowed for a calculation of the osmotic permeability coefficient (P(f); approximately 10(-3) cm/s) in line with reports in other epithelia. In addition, mannitol permeability (5.6 x 10(-6) cm/sec) was similar to that measured in "tight" epithelia, as determined by measurements of radiolabeled fluxes of the sugar across rabbit ciliary bodies mounted in the chambers used for the present fluid transport study. CONCLUSIONS: This work demonstrates that isolated ciliary epithelial preparations transport fluid in the blood-to-aqueous direction. The present observations suggest that mounting arrangements for measuring volumetric fluid flow across the ciliary epithelium is suitable for future studies directed toward the pharmacological control of secretion.

Animals↗

In vivo cAMP level in rabbit iris-ciliary body after topical epinephrine treatment.

PURPOSE: The present study estimates the in vivo cyclic AMP (cAMP) level in the rabbit iris-ciliary body after topical treatment with epinephrine. METHODS: Epinephrine 1% was applied unilaterally to pigmented rabbits. At selected time points between 10 min and 6 hr, a 2.5-mm diameter iris-ciliary body, in the treated eye, was irradiated with 2 J diode laser (2 W for 1 sec). Instant heat generated by the irradiation deactivated the cellular enzymes used in the synthesis and degradation of cAMP. Rabbits were sacrificed immediately, and samples of the iris-ciliary body were isolated from the irradiated area, the non-irradiated area, and from the contralateral, untreated eye. Levels of cAMP in these samples and in the aqueous humor were determined by radioimmunoassay. Further experiments were performed in rabbits pretreated with an alpha 2-adrenergic antagonist, yohimbine, and a beta-adrenergic antagonist, timolol, 30 min before the epinephrine treatment. Unilateral laser photocoagulation of the iris-ciliary body was performed at 10 min and 1 hr after the epinephrine treatment. RESULTS: The cAMP level in the photocoagulated iris-ciliary body did not change in parallel to the change in the aqueous humor. An increase of aqueous humor cAMP was observed for 6 hr. However, a reduction of cAMP level in the photocoagulated iris-ciliary body was observed at 1 hr after the epinephrine treatment. In yohimbine-pretreated rabbits, the reduction of cAMP level in the photocoagulated iris-ciliary body was absent. Pretreatment with timolol had no effect. CONCLUSIONS: These observations suggest that, at 1 hr after the epinephrine treatment, the cellular signal via the alpha 2-adrenergic receptors in the iris-ciliary body, which reduces the intracellular cAMP level, is stronger than that via the beta-adrenergic receptors.

Administration, Topical↗

[Regional differences in the ciliary body of cattle. An electron microscopy and histochemical study].

The bovine ciliary body was investigated by scanning and transmission electron microscopy. The number of cell organelles (mitochondria, rough endoplasmatic reticulum and Golgi complexes) of the nonpigmented (UPE) and the pigmented (PE) epithelium were quantitatively evaluated. Histochemically the activity of carbonic anhydrase (CA) and Na+/K(+)-ATPase was localized within the UPE and PE. As a result of this study, the bovine ciliary body was found to be organized similar to the human and primate ciliary body and can be divided into 4 zones: (1) transition zone between the iris and ciliary body; (2) prelenticular portion of the pars plicata; (3) postlenticular portion of the pars plicata; (4) pars plana. In zone 2 the UPE and PE are filled by numerous mitochondria and show extensive infoldings of the basal cell membranes, which react positively for CA and Na+/K(+)-ATPase, indicating that these cells are involved in the secretion of aequous humor. The transition zone is covered by extremely flat UPE cells and might influence the composition of the aqueous humor by reabsorption rather than secretion. In the postlenticular pars plicata, the number of mitochondria, membrane infoldings and enzyme activity decreases, while the number of rER and Golgi complexes, which are necessary for the synthesis of proteins and proteoglycans, increases. In the pars plana, the UPE is filled completely with filaments pointing to the mechanical strain caused by insertion of the zonular fibers.

Animals↗

Three-dimensional arrangement of collagen fibrils in human ciliary body.

The purpose of this study is to visualize the three-dimensional arrangement of collagen fibrils in aged human ciliary body and discuss their significance. The ciliary bodies obtained from two human eyes were treated with a NaOH cell-maceration method for 7 days, then prepared conventionally for light and scanning electron microscopy. The general morphology of the collagen tissue in the ciliary body appeared almost the same as that normally observed. Cellular elements were completely removed, but collagen fibrils were well preserved. In the stroma of the ciliary body, collagen fibrils were arranged irregularly. In the areas of the radial and circular ciliary muscles, considerable numbers of collagen fiber bundles were observed running in a circular direction. A honeycomb structure was seen in the pars plana, the walls and base of which were formed by interweaving collagen fibrils. The results suggested that collagen fibrils in the aged human ciliary body may be largely involved in the presbyopia.

Aged↗

Surgical management of melanocytoma of the ciliary body with extrascleral extension.

We treated four white women with extrascleral extension of suspected ciliary body melanomas with a modified block excision (three patients) or enucleation (one patient). Light and transmission electron microscopy established the diagnosis of ciliary body melanocytoma with extrascleral extension in each patient. Two eyes were irradiated before block excision. Block excision involved simultaneous removal of full-thickness cornea and sclera, iris, and ciliary body with tectonic corneoscleral grafting. The postoperative visual acuity of the three patients treated with a modified block excision was 20/25, 20/50, and 20/60, respectively. No patient experienced local tumor recurrence (30 to 60 months of follow-up). The two irradiated eyes eventually developed radiation-associated complications. After three years the other block excision patient had visual acuity of 20/25. Ciliary body melanocytoma should be included in the differential diagnosis of pigmented tumors of the anterior uvea with extrascleral extension. En bloc excision with simultaneous full-thickness corneoscleral resection is indicated in circumscribed ciliary body tumors, especially when extraocular extension is present.

Aged↗

Drug-induced ciliary body oedema: a new theory.

Drug-induced oedema of the ciliary body is rare, and occurs predominantly following exposure to sulphonamides. In a 31-year-old patient in her 37th week of pregnancy, we observed reversible myopia of -4.75 dioptres following the ingestion of chlorthalidone. In a second case report we describe, in a 61-year-old patient suffering from aspirin-sensitive asthma, recurrent ciliary body oedema with a marked spastic component which was triggered by the medications acetazolamide, dipivefrine and pilocarpine. We explain oedema of the ciliary body on the basis of the eicosanoids. We believe that the oedema is caused mainly by prostaglandins and that leucotrienes are predominantly responsible for the spastic component. We postulate a drug-induced elevation in eicosanoid concentrations, as well as certain interrelationships between ciliary body oedema and aspirin-sensitive asthma.

Acetazolamide↗

Ultrasound biomicroscopy of ciliary body cysts.

PURPOSE: To report the incidence and sector distribution of ciliary body cysts in normal subjects and to assess association with age using ultrasound biomicroscopy. METHODS: We prospectively examined 232 eyes of 116 normal subjects (51 men and 65 women) ranging in age from 15 to 84 years (mean +/- SD, 45.2 +/- 20.1). Complete ophthalmic examination, including gonioscopy and ophthalmoscopy with mydriasis, was performed. In addition, the circumference of the ciliary body was divided into eight sectors, and scanned in transverse and radial sections by high-resolution ultrasound biomicroscope to determine the incidence, distribution, and location of cysts. RESULTS: Based on one randomly chosen eye from each subject, cysts were detected in 63 (54.3%) of the 116 subjects. Cysts were found most frequently and in greater numbers in the inferior and temporal sectors. The incidence and the distribution range, expressed as the number of involved sectors per eye, were 73.1% and 3.8, respectively, for subjects 20 approximately 29 years old; both incidence and the number of involved sectors decreased with age (P = .0001). Cyst diameter ranged from 200 to 2500 microm; mean size decreased with age (P = .001). Gender and refractive error did not affect the incidence and distribution. There was significant bilateral correlation in the number, incidence, and distribution of ciliary body cysts. CONCLUSION: Ultrasound biomicroscopy disclosed a high incidence of ciliary body cysts in normal subjects, which decreased with age. Cysts were multiple and bilateral in many subjects.

Adolescent↗

Serotonin-accumulating cells in the iris-ciliary body and cornea of various species.

Serotonin was biochemically shown to be present in the iris-ciliary body of the frog, pigeon, goldfish and guinea-pig eyes at a concentration of between 55 and 95 ng per g. The aqueous fluid, in contrast, had no measurable serotonin, though a small amount of dopamine was present. Immunohistochemistry of the iris-ciliary body and cornea of all species failed to demonstrate the localization of serotonin. However, when tissues were first incubated with exogenous serotonin and then processed immunohistochemically for the localization of serotonin, positive staining was observed. Serotonin-accumulating fibres were present in the corneal stroma of the frog, pigeon and guinea-pig but not in the goldfish. In this species only a few unidentified non-neural cells in the corneal epithelium took up exogenous serotonin. The evidence of serotonin-accumulating fibres in the frog, rat or goldfish iris-ciliary body complex was not conclusive. This contrasted with the pigeon iris-ciliary body where there were some delicate fibres in the epithelium layers which take up exogenous serotonin. It is however, in the guinea-pig iris-ciliary body that the serotonin-accumulating cells are most numerous with fibres being situated in the muscular and epithelial areas. The distribution of tyrosine-hydroxylase immunoreactivity and serotonin-accumulating fibres in the guinea-pig iris-ciliary body was similar. The rat tissue also demonstrated a perfuse distribution of tyrosine-hydroxylase-positive fibres but lacked clear serotonin-accumulating fibres. The serotonin-accumulating fibres, therefore, do not give an indication of catecholaminergic fibres in all species.

Animals↗

[Symptomatic ciliary body melanocytoma: melanocytomalytic glaucoma].

CASE REPORT: A 33 year-old female with an asymptomatic pigmented mass in the iridocorneal angle of her right eye, arising from the ciliary body is presented. Ciliary body melanocytoma was suspected and conservative management recommended. After 36 months of follow-up the patient developed pain, inflammatory reaction and uncontrollable ocular hypertension, which was diagnosed as melanocytomalytic glaucoma. Tumor was removed by external iridecyclectomy and the histopathologic findings revealed necrotic melanocytoma. DISCUSSION: Ciliary body melanocytoma is a rare benign pigmented tumor that may present extension to the anterior chamber. Differential diagnosis mainly includes ciliary body melanoma, which carries a different prognosis and treatment.

Adult↗

Comparative anatomy of the ciliary body of the West Indian manatee (Trichechus manatus) and selected species.

OBJECTIVE: To examine the anatomy of the ciliary body in the West Indian manatee (Trichechus manatus), paying close attention to its vascularization and to compare to those of its distant relative, the African elephant (Loxodonta africana), the amphibious hippopotamus (Hippopotamus amphibius) and the aquatic short-finned pilot whale (Globicephala macrorhynchus). PROCEDURE: Specimens from each species were preserved in 10% buffered formalin, and observed stereomicroscopically before being embedded in paraffin, sectioned and stained by Masson trichrome, hematoxylin and eosin, and periodic acid-Schiff for light microscopic evaluation. RESULTS: The network of blood vessels in the ciliary processes of the West Indian manatee appear to have an intricate pattern, especially with regard to venous outflow. Those of the elephant are slightly less complex, while those of the hippopotamus and whale have different vascular patterns within the ciliary body. Musculature within the ciliary body is absent within the manatee and pilot whale. CONCLUSIONS: In general, there appears to be a direct relationship between the increased development of vasculature and the loss of musculature within the ciliary bodies of the aquatic and amphibious mammals presently studied. Specifically, the ciliary body of the West Indian manatee has a comparatively unique construction, especially with regard to its vasculature.

Animals↗