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The effect of hyaluronate on lysosomal enzyme activities in bovine ciliary body and iris was studied in vitro. Hyaluronates from both the human umbilical cord and bovine vitreous inhibited the activities of cathepsin B and acid phosphatase. Cathepsin D, beta-N-acetyl-glucosaminidase, beta-D-glucuronidase and alpha-L-fucosidase activities were not affected by the hyaluronate.
Clinical, histological, and electron-microscopic study of a leiomyoma of the ciliary body, which was removed by cyclectomy from the right eye of a 55-year-old female patient. This is the second case in the literature in which an excision has been performed and the diagnosis been confirmed by electron microscopy. The differential diagnosis between amelanotic malignant melanoma, schwannoma, and neurofibroma is discussed, and the electron-microscopic characteristics of a leiomyoma are demonstrated.
Delta 1-pyrroline-5-carboxylate dehydrogenase extracted from the combined ciliary body and iris of bovine eyes was studied biochemically. The enzyme was purified 120-fold. The partially purified enzyme had broad optimum at pH 8.0. Apparent Km values for DL-delta 1-pyrroline-5-carboxylate and NAD were 0.14 and 0.18 mM, respectively. The enzyme activity was strongly inhibited by GABA, proline, hydroxyproline, and glutamine.
This paper discusses direct coagulation of the ciliary body as a microsurgical method for treatment of hemorrhagic glaucoma. During a follow-up period of 6-12 months intraocular pressure was lowered in all cases from an average of 42.8 mm Hg. Of the 26 patients operated on, 25 were subsequently free of pain. Stabilization of visual acuity was achieved in two-thirds of the cases. The surgical procedure is simple and involves little risk.
OBJECTIVE: Mesectodermal leiomyoma of the ciliary body is a rare tumor with, to our knowledge, only 15 cases reported in the literature. It has a neural histopathologic appearance and a presumed origin from neural crest. DESIGN: Case report. RESULTS: Two cases of mesectodermal leiomyoma with histopathologic and immunohistochemical confirmation are reported. CONCLUSIONS: For the second time, we were able to demonstrate expression of neural immunohistochemical markers in this tumor.
To demonstrate the presence of mineralocorticoid receptors, specifically aldosterone receptors, iris-ciliary body cytosol from New Zealand albino rabbits was incubated with increasing amounts (0.5-20.0 nM) of radiolabeled aldosterone in the presence and absence of a 100-fold excess of aldosterone. A glucocorticoid receptor blocker, RU-28362, was employed when various steroids were allowed to compete with aldosterone for binding sites on the aldosterone receptor. Aldosterone bound to two classes of receptor proteins. Scatchard analysis of the data indicated one component to bind aldosterone with high affinity (Kd = 2.2 x 10-9 M) and low capacity (Bmax = 32 fmol/mg protein). If the concentration of aldosterone is increased, it also binds to a second component, but with a lower affinity (Kd = 9.8 x 10-9 M) and greater capacity (Bmax = 64 fmol/mg protein).
Electron microscopic observation of a mesectodermal leiomyoma of the ciliary body, in which clear perinuclear halos were present, revealed the ultrastructural characteristics of smooth muscle cells, which include myofilaments with fusiform densities, dense attachments, external lamina, and pinocytotic vesicles. In addition, fibrillary cytoplasmic processes containing large numbers of myofilaments with fusiform densities were notably arranged in a neurogenic pattern when observed under a light microscope. These are characteristic of and specific to mesectodermal leiomyomas. Masses or cords of large, polygonal cells with clear halos surrounding the large, round-to-oval nuclei were found to contain only a few myofilaments. Such features are atypical of mesectodermal leiomyomas. Melanocytes were scattered throughout the tumor, providing additional evidence for the neural crest theory of origination of mesectodermal leiomyomas, since melanocytes are well-recognized descendants of the neural crest. A small number of lipid droplets, abundant lysosomes, and, occasionally, phagosomes were also observed in the cells of this mesectodermal leiomyoma.
The objective of this study was to test the three novel ester derivatives of phenylephrone (isovaleryl, phenylacetyl, and pivalyl esters) as potential site-specific chemical delivery systems. The mydriatic effect and ocular distribution/metabolism of these compounds were studied by topical application to the eyes of normal rabbits. It was assumed that a reduction-hydrolysis sequence could produce the active phenylephrine in the iris-ciliary body tissues. All the derivatives showed a more pronounced mydriatic effect than that of phenylephrine, whereas phenylephrone was completely devoid of any mydriatic activity. Phenylacetyl ester was the most potent drug, with short duration of action, and showed maximum activity in the presence of 0.01% benzalkonium chloride without causing any visible irritation to the rabbit eye. Administration of the novel compounds to the eyes of the rabbits showed no traces of phenylephrine in the systemic circulation, contrary to topical administration of phenylephrine. Phenylephrone was detected in different compartments of the eye, whereas phenylephrine was present only in the iris-ciliary body tissues following administration of phenylacetyl ester. The conversion of phenylephrone esters to the active drug, phenylephrine, and thus their subsequent activity was dependent on the physicochemical characteristics of the drugs. The results suggest the potential use of phenylacetyl ester as a potent short-term mydriatic agent without systemic side effects.
In the anterior segment of the eye, phosphoinositides of the iris-ciliary body are the major source of AA for PG biosynthesis. In the past several years, we have demonstrated that these phospholipids are highly enriched in AA and have an extremely high metabolic turnover. We have also discovered that their metabolism by phospholipase C, which leads to the formation of IP3 and DG and the liberation of AA, is controlled by the following Ca2+-mobilizing receptors: alpha 1-adrenergic, M3- or M4-muscarinic cholinergic, substance P, and PGs. The release of IP3, DG, and AA in the iris was also demonstrated under in vivo conditions. Furthermore, it was demonstrated that this release is associated with denervation supersensitivity and subsensitivity of the iris. Two pathways have been demonstrated in the iris through which AA can be released directly from phosphoinositides: (a) Phosphoinositides can be hydrolyzed by phospholipase C, followed by hydrolysis of DG via lipases to liberate AA, and (b) AA can be released directly from phosphoinositides via phospholipase A2. Although the evidence for a link between Ca2+-mobilizing receptors and phospholipase C, via G proteins, has been well established, the precise link between these receptors and phospholipase A2 is still unclear. Our studies indicated that PGs may be involved in regulation of contraction and relaxation of the smooth muscles of the iris by increasing IP3 accumulation and consequently Ca2+ mobilization and by elevating the level of cAMP which in turn facilitates muscle relaxation. In addition, evidence of a link between the two pathways through the Ca2+ signaling system has been suggested. In the iris, PAF was found to liberate AA from phosphoinositides through the phospholipase A2, but not the phospholipase C pathway, thus emphasizing the role of this pathway in PG synthesis in the eye. These findings demonstrate that AA release and, consequently, PG synthesis in the iris of the eye are exquisitely regulated. In some species, such as bovine, cat and dog, PGs were found to act as full Ca2+ mobilizing agonists. It is possible that PGs function to maintain muscle tone in the resting iris smooth muscle cells, in addition to their involvement in various Ca2+-dependent processes. Our studies indicate that PGs may be involved in regulation of contraction and relaxation of the smooth muscles of the iris by increasing IP3 accumulation and consequently Ca2+ mobilization and by elevating the level of cAMP which in turn facilitates muscle relaxation.(ABSTRACT TRUNCATED AT 400 WORDS)
Mutations in the the glaucoma gene GCL1A, also known as trabecular meshwork glucocorticoid response (TIGR) or myocilin (Myoc), have been shown to be associated with juvenile-onset primary open-angle glaucoma. Very little is known about the pattern of expression of the TIGR gene in human ocular tissues. In-situ hybridization experiments demonstrated the localization of TIGR mRNA in cells throughout the iris, ciliary muscle, and the filtering portion of the trabecular meshwork of normal eye donors. The expression of TIGR protein was investigated by Western blot using an epitope-directed antibody to the carboxy terminus region of TIGR. This antibody was able to distinguish a recombinant TIGR fusion protein from a truncated TIGR form containing the naturally occurring Gln(368)-->stop mutation. In tissue extracts from the iris, ciliary body, and trabecular meshwork, the antibody recognized a major protein band of 57-kDa molecular mass. Deglycosylation treatment with PNGase F, NANase II, and O-glycosidase indicated that the 57-kDa protein in these tissues was unglycosylated. In agreement with this observation, in coupled in-vitro transcription/translation systems, the 57-kDa TIGR protein was unaffected by the presence of the processing and glycosylation activities of canine pancreatic microsomal membranes. These findings support the view that the expression of TIGR mRNA in cells of the iris, ciliary body, and trabecular meshwork correlates with that of TIGR protein, and that the 57-kDa TIGR protein was unglycosylated. These results, which are in contrast with earlier reports, raise the possibility that the TIGR protein might be processed into distinct forms in a tissue-specific manner.
Human muscarinic receptors comprise a family of five separate gene products, three of which (designated as M1, M2 and M3 subtypes) can be distinguished pharmacologically. Previous work indicates that sympathetic nerve terminals in the anterior uvea contain prejunctional muscarinic receptors that, upon activation by agonists, inhibit the neural release of norepinephrine. The aim of this study was to characterize the prejunctional effects of muscarinic agents on the electrically-evoked secretion of 3H-norepinephrine in isolated, superfused human iris-ciliary body tissue segments. Stimulation-evoked 3H-norepinephrine release was inhibited > 80% by carbachol and muscarine, but was unaffected by the M1-selective agonist McN A-343. Pilocarpine behaved as a partial agonist in this system, producing less than 40% of the maximum inhibition. The rank order of potency of selective antagonists at prejunctional muscarinic receptors was methoctramine (M2) > AF-DX 116 (M2) > pirenzepine (M1) > or = para-fluoro hexahydro-sila-definidol (M3). These data suggest that prejunctional muscarinic receptors in the human iris-ciliary body correspond to the M2 subtype. No evidence for age-related differences in prejunctional muscarinic receptor activity was seen in tissues obtained from 13 human donors, aged 10-83 years. Prejunctional muscarinic receptors may play a role in mediating the inhibitory effects of parasympathetic nerve stimulation or cholinomimetic drugs on ocular sympathetic neurotransmission in vivo.
Very little is known about the structure and development of the ciliary processes in the mouse eye. Our scanning electron microscope (SEM) studies reveal that, unlike other mammals, the ciliary processes form an irregular pattern, crossing over and interweaving rather than lying parallel to one another. Histological and SEM studies from embryonic day (E) 14.5 to postnatal day (P) 7 reveal that the first morphological sign of the ciliary zone is an annular bulge; this is then gradually molded to form discrete ciliary processes. The striking similarity between the developing capillary network and the adult ciliary folds suggests that the patterning template for the ciliary processes could be the underlying capillary network. Cell proliferation measurements and cell height assessments indicated that one of the first events occurring during the morphogenesis of ciliary processes is a proliferative surge around P0 in the outer ciliary epithelium. It is likely that this surge together with increasing cell heights leads to a bulging of this layer. After a slight delay, the inner ciliary epithelium responds by proliferating and extending inward toward the lens. Final shaping of the ciliary processes is achieved through cell height reductions in the inner ciliary epithelium. Thus, in the mouse, the temporal correlation between mitotic and cell height changes during ciliary body morphogenesis suggests that these processes play an integral role in the shaping of ciliary processes.
The binding of ten biotin-coupled lectins with different carbohydrate specificities to exfoliative material and neighbouring tissues was studied in 16 formalin-fixed and paraffin-embedded human eyes. Eight of the eyes were exfoliation positive while the rest were exfoliation negative. Exfoliative material reacted intensely with Lens culinaris (LCA), Canavalia ensiformis (ConA) and Ricinus communis (RCA-I) agglutinins. Positive reaction was also seen with wheat germ (WGA), peanut (PNA) and soybean (SBA) agglutinins. The superficial zonular lamella, zonular fibers and the non-pigmented epithelium of the ciliary body had a rather similar lectin-binding profile to exfoliative material. The lens capsule was essentially unreactive with all the lectins used. The lens epithelium reacted faintly with ConA, LCA, WGA and RCA-I. Pre-treatment with neuraminidase to remove sialic acid resulted in increased binding of PNA and SBA to exfoliative material, zonular fibers and the zonular lamella, and in decreased binding of WGA to the non-pigmented epithelium of the ciliary body, zonular fibers and the zonular lamella. The results indicate that alpha-mannosyl, beta-galactosyl, N-acetyl-D-glucosaminyl and N-acetylneuraminic acid residues are present in glycoconjugates of exfoliative material and neighbouring tissues.
PURPOSE: A subset of patients with anterior uveitis express the marker, perinuclear anti-neutrophil cytoplasmic antibody (pANCA). In this study, recombinantly isolated pANCA monoclonal antibodies were used to search for ocular cells expressing the pANCA antigen. METHODS: Paraffin sections of human ocular tissues obtained after death were analyzed by immunohistochemistry to identify cell types expressing pANCA antigen. Microdissected eye-bank ocular tissue was characterized by western blot analysis to confirm antigen expression and identify candidate protein species. RESULTS: Immunohistochemical analysis with pANCA monoclonal antibodies revealed cytoplasmic antigen expression in retinal ganglion cells and ciliary body epithelium. pANCA antigen expression was restricted to tissues bearing these cell types by western blot analysis. A common set of epitope-positive protein species was shared by the two tissues (28 kDa, 80 kDa, and 90 kDa). Comparison of ocular tissues from seven subjects revealed no heterogeneity in antigen expression. CONCLUSIONS: In this study, novel cytoplasmic antigens of the pANCA marker antibody expressed in ciliary body and retinal tissue were identified. Validation of these antigens as targets of inflammation in pANCA+ uveitis requires further biochemical and immunologic analysis.
Three juvenile patients showing a systemic disorder associated with small stature, brachydactyly and glaucoma were discovered to have spherophakia and a nanophthalmic axial length of the eye between 20.29 and 21.26 mm. According to clinical and radiological criteria only one patient was classified as having Marchesani syndrome; one patient suffered from an acrofacial disorder, and the third displayed typical ocular signs of Rieger syndrome. Pupillary block mechanism had led to glaucoma in all three patients. Despite iridectomy and trabeculotomy, two of them had unregulated intraocular pressure (IOP) and showed partial angleblock by progressive anterior synechiae after surgery. Ultrasonographic biomicroscopy revealed in all cases considerable hypoplasia of the ciliary body. We conclude that the clinical combination of spherophakia and brachydactyly is not necessarily limited to Marchesani syndrome. In the wide range of brachydactyly-associated syndromes an ophthalmic examination should always be performed in order to rule out ocular complications such as spherophakia and secondary glaucoma. We could not confirm Marchesani's hypothesis of a hyperplastic ciliary body in the spherophakia-brachydactyly syndrome, considering our nanophthalmic eyes. Pressure-reducing surgery in eyes with spherophakia and nanophthalmia seems to run a high risk of inducing an extensive formation of anterior synechiae.
Uveal melanoma mainly affects the choroid and to a lesser extent the ciliary body. Its clinical presentation, as well as the angiographic and microscopic features are often reported. Its macroscopic appearance is less often reported in publications, however. The macroscopic study of these tumors provides useful information and a series of photographs illustrating the macroscopic study of these tumors was gathered to be shown to ophthalmologists who have little experience with these intraocular tumors.
A benign adenoma of the pigment epithelium of the ciliary body in a 27-year-old woman simulated a malignant melanoma clinically and resulted in enucleation. The correct diagnosis was not made clinically despite the use of A- and B- scan ultrasonography and the radioactive phosphorus (32P) uptake test, procedures which are usually reliable in differentiating between melanoma and pseudomelanoma. We emphasize the shortcomings of these ancillary tests in differentiating pigment epithelial tumors from malignant melanoma.
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