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Biomedical subjects

O Nishi

Publications and source records attributed to O Nishi.

At least 37 records · Page 2Linked to original sources

Synthesis of interleukin-1, interleukin-6, and basic fibroblast growth factor by human cataract lens epithelial cells.

PURPOSE: To assay the following cytokines in an incubation medium of cultured lens epithelial cells (LECs) derived from human cataracts: interleukin-1 alpha (IL-1), interleukin (IL-6), basic fibroblast growth factor (b-FGF), tumor necrosis factor-alpha (TNF-alpha), and epidermal growth factor (EGF). SETTING: Nishi Eye Hospital, Jinshikai Medical Foundation, Osaka, Japan. METHODS: The anterior lens capsule with attached LECs was obtained by capsulotomy during cataract surgery and cultured. The incubation medium was changed on days 1 and 2 of culture and thereafter weekly up to 7 weeks. The media collected from a specific number of cultures at each medium change were pooled and assayed for cytokines by enzyme-linked immunosorbent assay. RESULTS: Interleukin-1 alpha was detected in one of the two pools of the 2 week cultures (207 pg/10(6) cells), in two of the three pools of the 3 week cultures (120 pg/10(6) and 139 pg/10(6) cells), and in one of the two pools of the 4 week cultures (111 pg/10(6) cells). Interleukin-6 was detected in one pool of the 1 week cultures (195 pg/10(5) cells) and in one pool of the 7 week cultures (81.6 pg/10(5) cells). Basic FGF was detected in the incubation media from three series of samples during the culture time course: 87 pg/ml in the 1 day cultures in the first series; 478, 310, and 269 pg/ml in the 1 day, 2 day, and 1 week cultures, respectively, in the second series; and 98 and 83 pg/ml in the 1 and 2 day cultures, respectively, in the third series. The TNF-alpha and EGF were not detected in any sample. CONCLUSION: After cataract surgery, IL-1, IL-6, and b-FGF may be produced in vivo by residual LECs, causing postoperative inflammation and LEC proliferation.

Cataract↗

Decreased prostaglandin E2 synthesis by lens epithelial cells cultured on heparin-surface-modified poly(methyl methacrylate).

PURPOSE: To evaluate whether heparin surface modification reduces prostaglandin E2 (PGE2) synthesis by lens epithelial cells (LECs) after intraocular lens (IOL) implantation. SETTING: Nishi Eye Hospital, Jinshikai Medical Foundation, Osaka, Japan. METHODS: The prostaglandin E2 (PGE2) concentration was determined in an incubation medium of human cataract LECs cultured on heparin-surface-modified (HSM) poly(methyl methacrylate) (PMMA) plates at 1, 2, 3, and 4 weeks of culture. A medium without heparin served as a control. RESULTS: The PGE2 concentration was significantly lower in the HSM than in the control medium at 3 and 4 weeks of culture. CONCLUSION: The results are consistent with the clinical observation of significantly decreased inflammation in eyes with HSM IOLs, indicating that such modification increases PMMA's biocompatibility with LECs.

Cataract↗

Inhibition of migrating lens epithelial cells by sustained release of ethylenediaminetetraacetic acid.

PURPOSE: To evaluate the effect of the sustained-release of ethylenediaminetetraacetic acid (EDTA) chelating Ca++ on lens epithelial cell (LEC) migration. SETTING: Nishi Eye Hospital, Jinshikai Medical Foundation, Osaka, Japan. METHODS: Polylactic-glycolic acid disks containing 10% EDTA were placed in saline solution for about 2 weeks in vitro. About 60% (7 micrograms/hour) of the EDTA was released during that time. The disks with a posterior chamber intraocular lens placed above were implanted in the capsular bag in five rabbit eyes after continuous curvilinear capsulorhexis and phacoemulsification. A disk without EDTA and the same lens type were placed in the bag in the contralateral eyes, which served as controls. RESULTS: After 2 to 3 months, opacification in the central posterior capsule was significantly reduced in all eyes that received the disk with EDTA. CONCLUSION: The deprivation of Ca++ disrupted interaction between the posterior capsule and migrating LECs by inactivating the adhesion molecule integrin synthesized by LECs, significantly reducing LEC migration onto the posterior capsule.

Animals↗

Explantation of endocapsular posterior chamber lens after spontaneous posterior dislocation.

The management of spontaneous posterior dislocation of an intraocular lens (IOL) (11.0 mm in overall diameter) encapsulated within the remaining lens capable is presented. The patient was a 55-year-old man who had had phacoemulsification following continuous curvilinear capsulotomy for monocular cataract 3 years earlier. The dislocated, encapsulated IOL was lifted up by hooking the fibrotic capsular opening with a bent disposable needle following vitrectomy and then explanted. A conventional posterior chamber lens with modified C-loops was inserted and sutured in the ciliary sulcus. This technique may be an alternative treatment for a posteriorly dislocated IOL. Histopathological examination clearly revealed that lens epithelial cell migration stopped at the planoconvex optic edge. This finding may be consistent with reports that the incidence of posterior capsule opacification with the planoconvex IOL is lower than with the bioconvex IOL.

Epithelium↗

Effects of the cytokines on the proliferation of and collagen synthesis by human cataract lens epithelial cells.

AIMS: To assess the effects of the cytokines, interleukin-1 (IL-1), IL-1 receptor antagonist (IL-1ra), transforming growth factor-beta 2 (TGF-beta 2) and basic fibroblast growth factor (b-FGF), on the mitosis of and collagen synthesis by lens epithelial cells (LECs) of human cataracts. METHODS: The anterior lens capsule with attached LECs was obtained by capsulotomy during cataract surgery and cultured. The cultures at 2 to 3 weeks before confluency were used for the experiments. To quantify the mitosis and collagen synthesis, the incorporation of 3H-thymidine and 3H-proline, respectively, into the LECs was measured by a scintillation counter at 48 hours and 24 hours, respectively, after addition of the cytokine at various concentrations into the incubation medium. RESULTS: IL-1 and b-FGF increased the mitosis and collagen synthesis significantly, but IL-1ra significantly decreased the mitosis while leaving the collagen synthesis intact. TGF-beta 2 decreased the mitosis significantly, but increased the collagen synthesis significantly. CONCLUSION: These cytokines may play an important role in an autocrine or paracrine pathway in the proliferation of residual LECs after cataract surgery. Elucidation of the role of these cytokines may lead to the development of new therapies for the prevention of secondary cataract.

Adult↗

Effects of platelet activating factor on mouse embryo implantation in vitro.

PURPOSE: Our purpose was to assess the role of platelet activating factor (PAF) in embryo implantation, we examined the effects of PAF and a PAF antagonist on the in vitro implantation of mouse embryos, using an in vitro embryo culture system in the absence of the endometrium. METHODS: BDF1 mouse pronuclear-stage embryos were cultured until they developed to the two-cell, the four- to eight-cell, or the morula stage in the absence of PAF or its antagonist CV6209. The medium was then changed and supplemented with PAF or CV6209 at various concentrations. We also examined the reversible effects of PAF addition to the media containing the PAF antagonist. RESULTS: The addition of PAF to the culture from the two-cell stage significantly (P < 0.05) increased the rates of embryo implantation in vitro (control, 69.8%; 10(-10) M PAF, 90.1%; 10(-9) M PAF, 95.5%). Similarly, the addition of PAF to the cultures from the four- to eight-cell and morula stage also significantly (P < 0.05) increased their rates of implantation in vitro. In contrast, the addition of CV6209 to the culture significantly (P < 0.01) decreased the rates of embryo implantation in vitro. CV6209 also decreased the rate of blastocyst formation. The degree of inhibition by CV6209 decreased with the advancing stage of embryos. The addition of PAF to media containing CV6209 reversed the inhibition and restored the implantation rate in vitro. CONCLUSIONS: These results suggest that PAF may act directly on the mouse embryo and favor its implantation like an autocrine activating factor, irrespective of the presence or absence of the endometrium.

Animals↗

Effect of indomethacin-coated posterior chamber intraocular lenses on postoperative inflammation and posterior capsule opacification.

We implanted indomethacin-coated intraocular lenses (IOLs) in rabbit eyes to ascertain how the sustained release of the drug affects postoperative inflammation and posterior capsule opacification (PCO). A preoperative resolution test showed that 1% indomethacin-coated IOLs placed in balanced salt solution released a mean 14.0 +/- 0.6 micrograms of the drug within 24 hours. Postoperatively, aqueous flare intensity in eyes with 0.1% indomethacin-coated IOLs and in eyes with 1.0% indomethacin-coated IOLs was significantly less at day 2 and at days 2 and 3, respectively, than in control eyes with uncoated lenses. In another group of eyes, histopathological examination showed that those with 1.0% indomethacin-coated lenses had significantly less PCO than the contralateral control eyes with uncoated IOLs.

Animals↗

Effects of diclofenac sodium and indomethacin on proliferation and collagen synthesis of lens epithelial cells in vitro.

We investigated the effects of diclofenac sodium and indomethacin on the proliferation of and collagen synthesis by lens epithelial cells (LECs) of human cataracts in culture. The anterior capsule with attached LECs, obtained by anterior capsulotomy during cataract surgery, was cultured directly without cell dispersion. When the culture became almost confluent, diclofenac sodium or indomethacin at various concentrations was added to the incubation medium. The incorporation of 3H-thymidine and 3H-proline into the LECs was measured after the cells were labeled with these radioactive materials. Both drugs greatly suppressed the incorporation of 3H-thymidine and of 3H-proline, indicating that they inhibit cell division and collagen synthesis by LECs. Both drugs may help prevent posterior capsule opacification.

Anti-Inflammatory Agents, Non-Steroidal↗

Effect of the cytokines on the prostaglandin E2 synthesis by lens epithelial cells of human cataracts.

BACKGROUND: Lens epithelial cells (LECs) derived from human cataracts have been reported to produce various cytokines and prostaglandin E2 (PGE2) in culture. The effects of IL-1, TGF-beta, and b-FGF on the PGE2 synthesis by LECs have been studied. METHODS: A circular piece of the anterior capsule with attached LECs was obtained by capsulotomy during cataract surgery and cultured. The primary, almost confluent, cultures were used for the study. The PGE2 concentration of the culture media for 24 h was measured after the addition of recombinant human IL-1 alpha, TGF-beta 2, or b-FGF at various concentrations. The PGE2 concentration was also measured in the media to which each cytokine and rabbit polyclonal anti-human antibodies against the corresponding cytokine had been added. RESULTS: The PGE2 concentration of the culture media after addition of IL-1 alpha at the concentration of 100 or 500 pg/ml (1765 (768) and 3071 (1121) pg/10(4) cells) or TGF-beta 2 at the concentration of 10 or 100 ng/ml (689 (264) and 750 (189) pg/10(4) cells) was significantly increased compared with that in the controls (67 (20) pg/10(4) cells). These effects were suppressed by the corresponding anticytokine antibodies. Basic FGF and anti-human b-FGF showed no significant effect on the PGE2 concentration. IL-1 and TGF-beta increased but b-FGF did not affect the PGE2 synthesis by LECs in culture. CONCLUSION: IL-1 and TGF-beta may participate in postoperative inflammation after cataract surgery by increasing PGE2 synthesis by residual LECs.

Cataract↗

Types of collagen synthesised by the lens epithelial cells of human cataracts.

AIMS/BACKGROUND: Residual lens epithelial cells (LECs) undergo fibrous proliferation after cataract surgery, resulting in capsular fibrosis. The purpose of this study was to determine the types of collagen produced in cultured LECs derived from human cataract LECs. METHODS: A circular section of the anterior capsule, about 5 mm in diameter, with LECs attached was obtained by anterior capsulotomy during cataract surgery and cultured directly without dispersion of the cells in a well, on the bottom of which a disc-shaped, thin plate of poly(methyl methacrylate) had been placed. At 5 to 6 weeks of culture, the proliferated cells of the culture were stained immunohistochemically with antibodies against human collagens I-VI by the avidin-biotin-peroxidase complex method. RESULTS: Collagens I, IV, V, and VI were positive in the cultured cells. Types IV and V were strongly present in almost all the cells whereas types I and VI were only observed in a few cells. Collagens II and III were negative. CONCLUSIONS: Since the lens capsule is known to be comprised of collagen IV, collagens I, V, and VI seem to be produced newly in culture. The capsular fibrosis seen after cataract surgery in vivo as a wound healing process of the lens capsule, may contain these types of collagens. The present culture model is useful for studying secondary cataract formation.

Cataract↗

Effect of interleukin 1 receptor antagonist on the blood-aqueous barrier after intraocular lens implantation.

Interleukin 1 (IL-1) possesses as an intercellular signal a wide spectrum of inflammatory, metabolic, haematopoetic, immunological, and reparative properties and can be a mediator not only of host defence but also of disease. Reduction of IL-1 can decrease the inflammatory host response. A human recombinant IL-1 receptor antagonist (IL-1ra) was used to block IL-1 after intraocular lens implantation in rabbits. Seventeen rabbits underwent intercapsular phacoemulsification and posterior chamber lens implantation. A 100 micrograms dose (0.1 ml) of IL-1ra (1 mg/ml) was injected into the anterior chamber at the end of surgery in seven rabbits. The 10 rabbits serving as the controls received no IL-1ra. Postoperatively, all rabbits were observed with a slit-lamp, and the aqueous flare intensity was measured with a laser flare cell meter at 12 hours, 1, 2, 3, and 4 days and thereafter at 1, 2, 3, and 4 weeks. Aqueous flare intensity was significantly lower on days 2 and 3, and fibrin deposition much less marked in the eyes treated with IL-1ra, compared with the controls. The results suggest that IL-1 is involved in the postoperative inflammation that occurs after intraocular lens implantation and the use of the IL-1ra would be valuable for reducing this problem.

Animals↗

Amplitudes of accommodation of primate lenses refilled with two types of inflatable endocapsular balloons.

OBJECTIVE: To investigate the maintenance of ocular accommodation by refilling the lenses of the eyes of youthful primates with inflatable endocapsular balloons. METHODS: The lenses of 21 cynomolgus monkeys were refilled following endocapsular phacoemulsification with a balloon that either approximates the shape of the non-accommodated lens or the accommodated crystalline lens. RESULTS: In nine of 15 successfully refilled lenses, we were able to perform automated refractometry to determine the amplitude of accommodation, ie, changes in refraction before and 1 hour after application of topical 4% pilocarpine hydrochloride to alter lens shape. At 2 weeks, 2 to 3 months, and 6 to 12 months after operation, mean (+/- SD) accommodation was 4.6 +/- 2.5, 2.5 +/- 0.5, and 1.7 +/- 0.7 diopters (D), respectively, in the lenses refilled with the nonaccommodation balloon (n = 5; preoperative value, 15.2 +/- 1.3 D), and it was 1.9 +/- 0.5, 1.3 +/- 0.9, and 1.8 +/- 0.9 D, respectively, in the lenses refilled with the accommodation balloon (n = 4; preoperative value, 17.0 +/- 2.9 D). CONCLUSION: The greater yield of accommodation with the nonaccommodation balloon is consistent with the recent theory on the mechanism of accommodation. Although the obtained accommodation was a small fraction of values determined prior to the operation and the small amplitude of accommodation decreased over time, the feasibility of refilling the lens with an inflatable endocapsular balloon, allowing at least some accommodation in the eyes of youthful primates, was demonstrated. Applied to humans, this procedure may allow accommodation following cataract surgery.

Accommodation, Ocular↗

Removal of lens epithelial cells following loosening of the junctional complex.

We previously reported a new method to remove residual lens epithelial cells--dispersion aspiration. The cells were loosened from their junctional complexes with Dispase, a proteolytic enzyme. To avoid intraocular tissue damage, the enzyme preparation was dissolved in sodium hyaluronate and injected into the capsular bag, which was carefully preserved during endocapsular cataract surgery. The cells were then removed by minimum irrigation/aspiration. In this study we incorporated ethylenediaminetetraacetic acid (EDTA), a calcium chelating agent for separating epithelial cells in tissue culture, into the procedure. The results of experiments in vitro and in rabbits suggest that this procedure also removed cells effectively with negligible damage to the zonules and corneal endothelium.

Animals↗

Intraocular lens encapsulation by shrinkage of the capsulorhexis opening.

A 57-year-old man with retinitis pigmentosa and subcapsular cataract had phacoemulsification with a continuous curvilinear capsulorhexis and implantation of a poly(methyl methacrylate) intraocular lens. Six months later, the patient presented with blurred vision and severe anterior capsule fibrosis which led to complete posterior chamber lens encapsulation.

Cataract↗

[Induction of prostaglandin E2 by interleukin 1 in human lens epithelial cells].

The authors proposed the hypothesis that pseudophakic inflammation, including the fibrin reaction, may be caused by interleukin (IL)-1, IL-6, other cytokines and/or prostaglandins (PGs), synthesized by residual lens epithelial cells (LEC). In testing our hypothesis, we have already detected IL-1 alpha, IL-6 and PGE2 in the culture media of human LEC obtained by capsulotomy during cataract surgery. In this paper, we studied the time course of PGE2-synthesis and interaction between IL-1 and PGE2. PGE2 concentration was measured by radioimmunoassay in the culture media to which rabbit antihuman IL-1 polyclonal antibody was added after culture for 6 h, 1 day, 1, 2, 3, 4, 5 and 6 weeks. There was no increase of PGE2, whereas in the untreated control culture media significant increase of PGE2 was confirmed. The results show that the antihuman IL-1 polyclonal antibody suppressed PGE2-synthesis. Thus, IL-1 induces PGE2 synthesis in human LEC culture.

Animals↗

Refilling the lens with a inflatable endocapsular balloon: surgical procedure in animal eyes.

In this report we describe the surgical details involved in refilling the lenses of 13 rabbit and 3 primate eyes using an inflatable endocapsular balloon to restore accommodation. The procedure involves endocapsular phacoemulsification through a small "buttonhole" or "dumbbell" anterior capsulotomy or minicircular capsulotomy and the simultaneous preservation of capsular integrity, including the zonules and ciliary muscles. An inflatable balloon made of thin silicone membrane is then inserted into the empty capsular bag. A liquid silicone polymer is injected into the balloon through a delivery tube, and the empty capsular bag is refilled by the inflated balloon. The procedure was found to be reproducible, and an accommodation of 6 D was confirmed in one primate eye. Capsular opacification occurred, but the proliferation and migration of residual lens epithelial cells could be hindered by abundant refilling. This lens-refilling technique may provide restoration of accommodation in future cataract surgery.

Accommodation, Ocular↗

Synthesis of interleukin-1 and prostaglandin E2 by lens epithelial cells of human cataracts.

To test our hypothesis that pseudophakic inflammation, including the fibrin reaction, may be caused by cytokines, prostaglandins (PG), or both, synthesised by residual lens epithelial cells (LECs), we measured interleukin-1 alpha (IL-1 alpha) and PGE2 in the incubation medium of cultures of human LECs obtained by capsulotomy during cataract surgery. After 1 week radioimmunoassay showed that there were 1.46 (0.62) ng of PGE2/10(6) cells (mean (SD) six cultures), and after 4 weeks, there were 5.50 (2.20) ng of PGE2/10(6) cells (seven cultures). During culture the cells proliferated and underwent fibroblast-like cell changes on exposure to the plastic of the wells. In the medium of control plates to which sodium diclofenac had been added PGE2 was not detected. Some IL-1 alpha was found in four of 10 samples, each of which contained media from 12 cultures; 207 pg/10(6) cells in one of the two pools of 2-week cultures, 120 pg/10(6) cells in one pool and 139 pg/10(6) cells in another of the three pools of 3-week cultures, and 111 pg/10(6) cells in the one pool of 4-week cultures. PGE2 and IL-1 alpha may therefore be produced in vivo by residual LECs after cataract surgery, and may be involved in postoperative inflammation, including the fibrin reaction.

Cataract↗