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Characterization of human and rabbit pigmented and nonpigmented ciliary body epithelium.

Nonpigmented epithelial (NPE) and pigmented epithelial (PE) cells were carefully dissected from both human and rabbit ciliary processes and have been maintained in vitro and partially characterized by morphology and immunocytochemical techniques using polyclonal and monoclonal antibodies against S-100 proteins, collagen type I and type III. The tissue distribution of these proteins was studied in formalin fixed deparaffinized tissue sections of human and rabbit eyes by immunoperoxidase staining techniques. Both NPE and PE cell lines from human and rabbit showed hexagonal morphology by light microscopy; distinct granules containing pigment could be visualized in the PE cell lines, but not in the NPE cells. Antibodies against S-100 proteins stained NPE layer intensely and PE layer slightly in the human tissue sections. The staining was less intense in rabbit tissues than human tissues. The ciliary body stroma was positive for collagen type III and negative for collagen type I or S-100.

Animals↗

[Light and electron microscopy studies of the development of the human ciliary body].

In human embryos and fetuses with a gestation age of 9.5 to 24 weeks, differentiation of the ciliary muscle was examined by both light and transmission electron microscopy, and the surface morphology of the ciliary body was analyzed by scanning electron microscopy. Smooth muscle cells develop from mesenchymal elements or early fibroblasts located at the anterior rim of the optic cup. Musclelike cells exhibiting dense bodies and myofilaments were first distinguished during week 12 and smooth muscle cells with an adultlike appearance become apparent during week 15/16. A cellular maturation process can be observed up to week 22. Fibroblasts separating the muscle cell layers from each other also derive from the same precursor cells, as do smooth muscle cells, thereby pointing out the close relationship between the two cell types. The first radial ciliary folds could be observed at week 10.3 by scanning electron microscopy. However, true ciliary processes have only been described at week 24. The ciliary processes observed during week 24 only differed from those of the adult eye by the dimensions and lack of surface infoldings. A primitive pars plana was first identified during week 24. The morphological basis for aqueous humor production is discussed.

Ciliary Body↗

Metastatic disease from untreated choroidal and ciliary body melanomas.

We report the case histories of three patients with untreated malignant melanoma of the choroid or ciliary body. Metastatic disease which resulted in death was diagnosed four years in two patients and 13 years in one patient after the diagnosis of choroidal melanoma was suspected. The diagnosis of malignant melanoma was confirmed by histopathology in two of these patients.

Choroid Neoplasms↗

Malignant melanoma of ciliary body: a case report.

Ocular malignant melanomas are infrequently seen in Indian patents and most them involve the choroid. Ciliary body malignant melanoma is rather rare. This case report illustrates an occurrence in an Indian patient.

Aged↗

Identification of genes expressed in retinal progenitor/stem cell colonies isolated from the ocular ciliary body of adult mice.

Rare pigmented cells showing retinal stem cell characteristics have been identified in the ocular ciliary body (CB) of adult mammals. In vitro, these cells were reported to clonally proliferate and generate pigmented sphere colonies (PSC) containing multipotent retinal progenitor-like cells. Because these cells may have important clinical applications and because their embryonic origin is unclear, we have analyzed their local environment and gene expression profile. We found that transcription factors Pax6, Six3, and Rx, all involved in early eye morphogenesis, were expressed in the CB of adult mice. By sequencing a PSC cDNA library, we found that PSC expressed at high levels transcripts involved in the control of redox metabolism and cellular proliferation. PSC also expressed the retinal transcription factor Six6, which expression was not detected in the CB epithelium. By in situ hybridization screen, we found that Palmdelphin (Palm), Hmga2, and a novel transcript were expressed in the central nervous system of early embryos. Palm expression delineated the pigmented epithelium of the future CB and the developing myotome. Hmga2 was expressed in the ventricular zone of the telencephalon, the developing retinal ciliary margin and lens. Several genes expressed in PSC were also expressed in the nasal anlagen. Taken together, our study reveals that PSC isolated from the ocular CB express genes involved in the control of embryonic development, retinal identity, redox metabolism, and cellular proliferation.

Animals↗

Reappraisal of Callender's spindle a type of malignant melanoma of choroid and ciliary body.

A follow-up study and histologic reevaluation were made of 105 melanomas of the choroid and ciliary body that had originally been classified as Callender's spindle A type. There were 18 deaths attributable to tumor, with metastatic disease confirmed by autopsy or biopsy in eight cases. We were able to separate the 105 melanomas histopathologically into three groups. The first group consisted of 15 cases in which the spindle-shaped tumor cells were cytologically benign; no deaths were observed for this group. The 75 tumors in the second group were composed of spindle cells, but differed from those in the first group by their malignant features, namely, more atypicality of cells, mitotic activity, necrosis, invasion into sclera or through Bruch's membrane, larger size of the tumor, or any combination of the above. The prognosis for this group was good, comparable to that of spindle B melanomas. The 15 tumors in the third group contained epithelioid cells and had a poor prognosis, comparable to that of mixed-cell melanomas.

Choroid Neoplasms↗

Natural course and histopathologic findings of lacrimal gland choristoma of the iris and ciliary body.

PURPOSE: To show a well-documented clinicopathologic correlation of lacrimal gland choristoma of the iris and ciliary body, to review the literature on the subject, and to recommend treatment of this condition. METHODS: A congenital iridociliary mass was removed by iridocyclectomy when a female infant was 19 months old because it had produced a large cyst, secondary glaucoma, a vascularized corneal pannus, focal cataract, and iris heterochromia secondary to pigment dispersion. The excised mass was studied by routine histopathologic methods. RESULTS: The mass proved histopathologically to be a lacrimal gland choristoma composed of mature lacrimal gland tissue associated with a large epithelial-lined cyst and several smaller cysts. Postoperatively, the glaucoma resolved and the child had visual acuity of 20/40 14 months after surgery. CONCLUSIONS: Lacrimal gland choristoma of the anterior uvea has typical clinical features that should indicate that correct diagnosis. It is a fleshy, often cystic, lesion with an irregular, cerebriform surface that appears identical to the lacrimal gland in the orbit. Although the mass itself is generally stable, secondary cysts in the lesion can enlarge and secondary glaucoma and other complications can develop. Consequently, affected patients should be followed up at close intervals and surgical excision performed if such complications begin to develop.

Choristoma↗

Prognostic factors in choroidal and ciliary body melanomas with extrascleral extension.

In a retrospective study, 50 (8.2%) of 610 patients with malignant melanoma of the ciliary body or choroid had extrascleral extension. Of 46 patients for whom follow-up data were available, 24 (52%) survived five years, 20 (42%) survived ten years, and 17 (37%) survived 15 years. Factors that seemed to affect survival significantly included intraocular tumor size and extraocular tumor size and location. Our observations did not support the role of primary exenteration. Five patients (11%) with extrascleral extension had orbital recurrences and all died within 31 months of surgery regardless of treatment.

Adult↗

Mesectodermal leiomyoma of the ciliary body: new evidence for neural crest origin.

An 8-year-old white boy had a mass of the ciliary body in his left eye. Both the translucent characteristics and the magnetic resonance imaging findings suggested that this lesion was cystic. Fluid aspiration biopsy and iridocyclectomy were performed. By light microscopy the neoplasm showed the characteristic appearance of a neuroid tumor; however, on electron microscopic examination, the tumor exhibited characteristic features of a smooth muscle neoplasm and was diagnosed as a mesectodermal leiomyoma. Observation of melanin granules in scattered tumor cells further confirmed that the tumor had the same origin as uveal melanocytes, which also derive from the neural crest.

Biopsy, Needle↗

Binding of CGRP analogs and their effect on adenylate cyclase activity in porcine iris-ciliary body.

The structure-activity relationship of the calcitonin gene-related peptide (CGRP) in the porcine iris-ciliary body was studied using different CGRP analogs. The receptor binding affinity is located mainly in the carboxyterminal end of the CGRP peptide while the ability to stimulate adenylate cyclase (AC) enzyme is mainly in the aminoterminal end of the peptide. The binding of CGRP analogs was also found to be temperature-dependent. Changes in the alpha-helical region or in the beta-turn, as well as replacements of threonine-4, asparagine-25 or asparagine-26, reduce the binding affinity already at +4 degrees C. Truncated aminoterminus, changes in the loop region between cysteines 2 and 7, and especially in threonine 6, have for their part an important role in maintaining AC-stimulating activity.

Adenylyl Cyclases↗

Matched group study of preenucleation radiotherapy versus enucleation alone for primary malignant melanoma of the choroid and ciliary body.

We report the results of a nonrandomized, matched group survival study comparing 29 patients with a choroidal or ciliary body melanoma managed by enucleation alone to 29 patients managed by enucleation following external beam ocular irradiation (20 Gy in five fractions over 5-7 days just prior to enucleation). Variables on which the patients in the two groups were matched included age at time of enucleation, largest linear tumor dimension, location of the anterior tumor margin relative to the equator and ora serrata, melanoma cell type, and extrascleral tumor extension. The cumulative 5-year survival in the enucleation alone group was 57.9% (SE = 9.9%), whereas that in the preenucleation radiation therapy group was 63.9% (SE = 12.2%). This difference is not statistically significant (p greater than 0.5, Mantel-Haenszel test). The authors discuss the strengths and limitations of their study and the implications of their results.

Adult↗

Extracellular ATP effects on calcium signaling in cultured human non-pigmented ciliary body epithelium.

PURPOSE: To determine the effects of extracellular ATP on calcium signaling in cultured human non-pigmented ciliary body epithelium (HNPE). METHODS: Intracellular calcium (Ca(2+)(i)) was measured using spectrofluorescence video microscopy in isolated HNPE cells loaded with the fluorescent dye Fura-2. RESULTS: Nucleotides caused a transient oscillatory increase in Ca(2+)(i) with a potency order of ATP = UTP > ADP > AMP> alpha,beta-methylene-ATP. Treatment with thapsigargin (100 nM), an inhibitor of endoplasmic Ca(2+)-ATPase pumps, produced a sustained increase in Ca(2+)(i). Subsequent exposure to ATP caused a rapid reduction in Ca(2+)(i) and this effect was reduced by pre-exposure to vanadate and to a lesser extent in sodium free solution. Prolonged exposure to ATP in the presence of thapsigargin caused a transient spike increase in Ca(2+)(i) which was prevented by exposure to low extracellular Ca(2+) (1 nmol/l), verapamil, nifedipine or the microfilament disrupting agent, cytochalasin B. CONCLUSIONS: These results provide evidence for ATP mobilisation of Ca(2+) from intracellular stores via P2Y2 receptor activation in HNPE cells. ATP also primarily activates a vanadate-sensitive Ca(2+ )-ATPase pump, in addition to having a smaller effect on the Na( +)/ Ca(2+) exchanger in terminating the calcium signal. Capacitative calcium entry, possibly via an L-type Ca(2+) channel, is implicated in generating a calcium signal following emptying of intracellular stores and is sensitive to cytoskeleton disruption. ATP can thus regulate a potent intracellular signal for secretion, suggest-ing that purinergic receptors may provide a therapeutic target in glaucoma.

Adenosine Triphosphate↗

Is active glucose transport present in bovine ciliary body epithelium?

Hyperglycemia is a major risk factor for diabetic cataract formation. Effective regulation of glucose transport by the ciliary body epithelium (CBE) is pivotal to normal glycemic control in the anterior eye, which in turn affects the glucose level of the crystalline lens. The present study aimed to characterize the glucose transport mechanisms across the bovine blood-aqueous barrier (BAB) represented by the CBE. With an Ussing-type chamber, the glucose transport kinetics were measured and characterized in the presence and absence of various glucose transporter inhibitors. The saturation characteristics of the CBE to glucose were estimated from an Eadie-Hofstee plot. The mRNA expression of glucose transporters in specific regions of the bovine CBE was assessed using RT-PCR. The trans-CBE glucose flux was found to be sensitive to the glucose transporter inhibitors cytochalasin B, phloretin, and phlorizin. The transport system had a kinetic constant of 5.3 mM and a maximum velocity of 349.5 nmol.h(-1).cm(-2). Gene expression for GLUT1, GLUT3, GLUT4, GLUT5, and SGLT2 was observed in both the pars plana and pars plicata regions of the bovine CBE. This study demonstrates that glucose transport across the bovine CBE is primarily passive in nature. However, the novel findings of 1) the presence of a phlorizin-sensitive glucose flux and 2) gene expression for SGLT2 mean that a potential role for active glucose transport cannot be ruled out. The elucidation of the exact function of SGLT2 in the bovine CBE may shed important light on the glucose transport and physiology of the BAB and inform future studies of glycemic control in relation to diabetic cataract formation.

Animals↗