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Shigeaki Ohno

Publications and source records attributed to Shigeaki Ohno.

At least 37 records · Page 2Linked to original sources

[A case of posterior scleritis associated with extensive retinochoroidal atrophy].

BACKGROUND: Posterior scleritis is known to exhibit various changes in the ocular fundus, but retinochoroidal atrophy is a rare complication. CASE: A 54-year-old man presented with the complaint of blurred vision in the right eye. The patient had visited our clinic twice before, 22 and 11 years earlier. Although his funduscopic findings had demonstrated choroidal detachment in both eyes, the cause could not be determined at that time. FINDINGS: His visual acuity was 20/200, OD and 20/100, OS. Funduscopic examination showed annual choroidal detachments and geographic retinochoroidal atrophy in the posterior pole OU, and serous retinal detachment OD. B-scan ultrasonograpy revealed diffuse thickening and flattening of the posterior coats of the eye, and orbital enhanced computed tomography revealed thickening and enhancement of the posterior sclera. A diagnosis of posterior scleritis was made. Prednisolone 80 mg/ day was initiated and gradually tapered. Nine months later choroidal and serous retinal detachment were resolved. CONCLUSION: We encountered a rare case of posterior scleritis with associated extensive retinochoroidal atrophy. We speculated that the cause was inflammation of the retina and choroid, and accumulation of subretinal fluid for a long period.

Atrophy↗

Phosphorylation of p27(KIP1) in lens epithelial cells after extraction of fiber cells.

Opacification of the posterior capsule depends on replication of the residual lens epithelial cells lining the capsule. However, the mechanisms in the regulation of lens cell proliferation have not been determined. The purpose of this study is to examine the expression of p27(KIP1), a cyclin-dependent kinase inhibitor, and its phosphorylation, and cyclin D1 in lens epithelial cells after extraction of fiber cells. C57Bl6 mice (12 weeks old) were anesthetized, and the lens fiber cells were surgically extracted. Eyeballs were collected and fixed at 15 min and 24 h after extraction with and without injection of a specific phosphorylated extracellular signal-regulated kinase (pERK) 1/2 inhibitor (PD98059) to the anterior chamber. Collected tissues were analyzed using immunohistochemistry with anti-p27(KIP1), anti-phosphorylated p27(KIP1) on serine 10 (s10-phospho-p27) and cyclin D1 antibodies. Human lens epithelial cells were cultured, and then were treated with and without 40 ng/ml human recombinant basic fibroblast growth factor (bFGF), which was analyzed by Western blot analysis. In the untreated lens, p27(KIP1) was not phosphorylated in the lens epithelial cells, although p27(KIP1)-positive nuclei were detected in the lens cells of the equatorial region. Immunoreactivity for cyclin D1 was hardly detected in the lens. Nuclear immunoreactivity for p27(KIP1) and s10-phospho-p27 was observed in several lens cells of the equatorial region 15 min after extraction of fiber cells. Western blotting demonstrated that the p27(KIP1) phosphorylation form was upregulated 15 min after bFGF treatment in cultured lens epithelial cells. Many cyclin D1-positive nuclei were noted 24 h after the surgery. p27(KIP1) phosphorylation and cyclin D1 induction were inhibited by PD98059. s10-phospho-p27 and p27(KIP1) immunoreactivity was undetected in the lens cells 24 h after the extraction of fiber cells. It is possible that the phosphorylation of p27(KIP1), and cyclin D1 expression are regulated by the ERK pathway in lens cells after the extraction of fiber cells.

Animals↗

[Different outcome among eyes with proliferative diabetic retinopathy indicated for vitrectomy].

PURPOSE: The postoperative outcome was evaluated in each group of surgical indications of vitreous surgery for proliferative diabetic retinopathy (PDR), to investigate the factors responsible for postoperative visual prognosis. METHODS: Primary vitrectomy was performed in 119 eyes of 92 patients with PDR. Average postoperative follow-up period was 19 months. The indications for vitrectomy included vitrous hemorrhage in 58 eyes, macular tractional retinal detachment in 17 eyes, extramacular tractional retinal detachment in 10 eyes, macular heterotopia in 11 eyes, and progressive fibrovascular proliferation in the posterior fundus in 23 eyes. RESULTS: The visual acuity finally improved by 2 lines or more in 91 eyes (77%), remained unchanged in 10 eyes (8 %), and decreased by 2 lines or more in 18 eyes (15%). Final postoperative visual acuity was significantly better in cases of vitreous hemorrhage or progressive fibrovascular proliferation in the posterior fundus than in others. Preoperative rubeosis iridis and macular tractional retinal detachment were probably responsible for the final visual impairment, and intraocular tamponade affected the difference in visual prognosis between the groups of surgical indication. Multivariate analysis in all cases revealed that factors influencing visual outcome were preoperative rubeosis iridis and anemia. CONCLUSION: Rubeosis iridis and macular tractional retinal detachment were prognostic factors of the surgery. Vitrectomy for PDR may be effective in improving postoperative visual acuity if performed in the early stage of progressive fibrovascular proliferation in the posterior fundus after sufficient retinal photocoagulation.

Adult↗

Effect of p75NTR on the regulation of photoreceptor apoptosis in the rd mouse.

PURPOSE: Apoptosis is the final common pathway for photoreceptors in several forms of retinitis pigmentosa. Recent study has shown that continuous light exposure upregulates low-affinity neurotrophin receptor p75 (p75NTR), which is involved in light-induced photoreceptor apoptosis in rat retina. However, the function of p75NTR in inherited forms of photoreceptor degeneration has not yet been examined. This study was conducted to elucidate the potential role of p75NTR in the rd mouse, one of the best characterized animal models of retinitis pigmentosa. METHODS: Double-mutant (rd/rd, p75NTR-/-) mice were crossbred from rd/rd and p75NTR-/- mice. Retinas from control (+/+, p75NTR+/+; rd/rd, p75NTR+/+; rd/rd, p75NTR+/-), and double-mutant (rd/rd, p75NTR-/-) mice were examined by light microscopy and TdT-mediated dUTP nick end labeling (TUNEL) from postnatal day (P)9 through P20. p75NTR mRNA expression in +/+, p75NTR+/+, and rd/rd, p75NTR+/+ mice were examined by real-time PCR analysis. p75NTR protein expression in +/+, p75NTR+/+; rd/rd, p75NTR+/+; and rd/rd, p75NTR-/- mice were examined by immunohistochemistry. RESULTS: p75NTR mRNA expression in rd/rd, p75NTR+/+ mice was significantly upregulated compared with +/+, p75NTR+/+ mice at P13 and P20. p75NTR protein expression was observed mainly in Müller glial cells, and its expression was upregulated in the outer nuclear layer during photoreceptor degeneration. However, histochemical analyses showed that the time course of retinal degeneration and the extent of photoreceptor apoptosis in rd/rd, p75NTR-/- double-mutant mice was indistinguishable from that in rd mice carrying functional p75NTR (rd/rd, p75NTR+/+, and rd/rd, p75NTR+/-). CONCLUSIONS: These results suggest that in contrast to its role in light-induced photoreceptor degeneration, p75NTR is not essential for apoptosis in the rd mouse.

Animals↗

Increase in macrophage migration inhibitory factor levels in lacrimal fluid of patients with severe atopic dermatitis.

BACKGROUND AND AIMS OF THE STUDY: Atopic dermatitis is a chronic inflammatory skin disorder that often involves some ophthalmic features. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that is associated with the generation of cell-mediated immune responses. Although serum MIF levels may be elevated in severe atopic dermatitis, the quantity of MIF in regional ocular fluid remains unknown. We measured MIF levels in tears (lacrimal fluid) of patients with atopic dermatitis. PATIENTS AND METHODS: Tear samples were collected from 16 patients with atopic dermatitis, 10 patients with allergic conjunctivitis, and 15 healthy control subjects. The clinical severity of atopic dermatitis was evaluated according to the Scoring Atopic Dermatitis (SCORAD) index. The index was calculated by summing the following scores: extent criteria, intensity criteria, and subjective symptoms. Macrophage migration inhibitory factor levels were determined by a human MIF enzyme-linked immunosorbent assay. All comparisons were two-tailed, and P values <0.01 were considered as statistically significant. RESULTS: The mean MIF concentration in lacrimal fluid collected from healthy control subjects was 0.69+/-0.2 ng/ml. The mean tear MIF levels were 17.87+/-6.3 ng/ml in moderate-to-severe atopic dermatitis (SCORAD> or =15, P=0.002), 0.93+/-0.08 ng/ml in mild atopic dermatitis (SCORAD<15), and 2.76+/-0.86 ng/ml in allergic conjunctivitis (P=0.008). CONCLUSIONS: A proinflammatory cytokine MIF level was elevated in tears as well as serum in cases of severe atopic dermatitis. These results suggest that MIF may play an important role in the induction or enhancement of ophthalmic features related to severe atopic dermatitis.

Adolescent↗

Immunolocalization of cyclin D1 in the developing lens of c-maf -/- mice.

The maf gene encodes a transcription factor protein containing a typical basic/leucine zipper domain structure, a motif for protein dimerization and DNA binding. It has been demonstrated that maf family genes have important roles in embryonic development and cellular differentiation. In this study, localization of cyclin D1, one of the cell cycle-related molecules, was examined immunohistochemically in developing lens cells of c-maf knockout (-/-) mice. At embryonic day 14 in wild-type mice, lens cells consisted of round epithelial cells in a single layer and regularly arranged elongated lens cells, indicating primary lens fiber cells. Cyclin D1-positive nuclei were observed in the lens epithelial cells, whereas cyclin D1 was not detected in the primary lens fiber cells. In c-maf -/- mice, a variety of round epithelial cells were located in the anterior and posterior lens. Many cyclin D1-positive nuclei were observed in lens epithelial cells as well as posterior lens cells. These results are consistent with c-maf playing a role in the regulation of cyclin D1 in developing lens cells.

Animals↗

Effects of blue honeysuckle (Lonicera caerulea L.) extract on lipopolysaccharide-induced inflammation in vitro and in vivo.

The aim of the present study was to investigate the effects of blue honeysuckle extract (BHE), which contains high level of phenolic compounds, on endotoxin-induced uveitis (EIU). Male Lewis rats were randomly divided into 5 groups with 14 rats in each (eight rats for collection of aqueous humor, six rats for histologic examination). EIU was induced by a footpad injection of lipopolysaccharide (LPS). 1, 10, or 100 mg of BHE was injected intravenously immediately after LPS injection. The aqueous humor was collected at 24 h after LPS injection, the number of infiltrating cells, protein concentration, nitric oxide (NO), tumor necrosis factor (TNF)-alpha, and prostaglandin (PG)-E2 levels in the aqueous humor were determined. Some eyes were enucleated for histologic examination and immunohistochemical analysis. Immunohistochemical staining with a monoclonal antibody against activated nuclear factor (NF)-kappaB was performed to evaluate the effect of BHE on NF-kappaB activation. To further clarify the anti-inflammatory effect, RAW264.7 cells (a mouse macrophage cell line) were stimulated with LPS in the presence or absence of BHE and its major phenolics, cyanidin 3-glucoside (C3G), cyanidin 3-rutinoside (C3R), chlorogenic acid (CA). Expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) were analyzed by Western blot method. BHE treatment significantly reduced the inflammatory cell infiltration, the protein concentration, the levels of NO, TNF-alpha and PGE2 in the aqueous humor and improved histologic status of the ocular tissue. The number of activated NF-kappaB-positive cells was lower in the iris-ciliary body treated with BHE at 3 h after LPS injection. BHE significantly suppressed the production of NO, PGE2 and TNF-alpha in the culture medium as well as the expression of iNOS and COX-2 by LPS-stimulated RAW264.7 cells in a dose-dependent fashion. C3G, C3R and CA showed no or weak inhibitory effects on the level of inflammatory mediators and the expression of iNOS and COX-2. These results suggest that BHE attenuates the degree of inflammation in eyes with EIU by inhibiting the NF-kappaB dependent signaling pathway and the subsequent production of proinflammatory mediators.

Animals↗

Suppressive effects of astaxanthin against rat endotoxin-induced uveitis by inhibiting the NF-kappaB signaling pathway.

We investigated the effects of astaxanthin (AST), a carotenoid, on endotoxin-induced uveitis (EIU), and over the course of the disease measured the expression of inflammatory cytokines and chemokines in the presence or absence of AST. EIU was induced in male Lewis rats by footpad injection of lipopolysaccharide (LPS). The animals were randomly divided to 12 groups with eight animals in each. Immediately after the inoculation, AST (1, 10, or 100 mg kg(-1)) was injected intravenously. Aqueous humour was collected at 6, 12 and 24 hr after LPS inoculation and the number of infiltrating cells in the anterior chamber was counted. In addition, we assayed the concentration of protein, nitric oxide (NO), tumour necrosis factor-alpha (TNF-alpha) and prostaglandin E2 (PGE2). Immunohistochemical staining with a monoclonal antibody against activated NF-kappaB was performed in order to evaluate the effects of AST on NF-kappaB activation. Rats injected with AST showed a significant decrease in the number of infiltrating cells in the anterior chamber and additionally there was a significantly lower concentration of protein, NO, TNF-alpha and PGE2 in the aqueous humour. Moreover, even early stages of EIU were suppressed by injection of AST. The number of activated NF-kappaB-positive cells was lower in iris-ciliary bodies treated with 10 or 100 mg kg(-1) AST at 3 hr after LPS injection. These results suggest that AST reduces ocular inflammation in eyes with EIU by downregulating proinflammatory factors and by inhibiting the NF-kappaB-dependent signaling pathway.

Adjuvants, Immunologic↗

Usefulness of quantifying serum KL-6 levels in the follow-up of uveitic patients with sarcoidosis.

BACKGROUND: KL-6 is a human glycoprotein secreted by type II alveolar cells in the lung, and its serum levels increase in pneumonia of various causes. We previously reported that serum KL-6 levels in uveitis patients with sarcoidosis were significantly higher than those of other uveitis patients and healthy controls. Additionally, the combined measurement of serum KL-6 and angiotensin converting enzyme (ACE) was useful for screening uveitic patients to diagnose sarcoidosis. The purpose of the present study was to investigate the clinical usefulness of quantifying serum KL-6 levels for following-up the patients with sarcoidosis. METHODS: Sera were obtained from 36 uveitic patients diagnosed with sarcoidosis and the same number of healthy volunteers. To examine the influence of systemic medication, we also collected blood samples from four more sarcoidosis patients, who were systemically treated with corticosteroid or angiotensin converting enzyme (ACE) inhibitor, an anti-hypertensive drug. The serum concentration of KL-6 was measured by a human KL-6 electrochemiluminescence immunoassay (ECLIA). RESULTS: The mean KL-6 concentrations of sarcoidosis patients and healthy controls were 449.3+/-66.3 (mean+/-SE) and 192.1+/-11.3, respectively. The average levels of serum KL-6 were significantly elevated in sarcoidosis patients compared with healthy control subjects (P<0.001), and there were significant correlations between serum KL-6 and ACE levels in the patients with sarcoidosis (r=0.70 and P<0.0001). Moreover, serum KL-6 concentrations were less affected by systemic corticosteroid, and unaffected by ACE inhibitory drugs in contrast to ACE levels. CONCLUSIONS: Measurement of serum KL-6 in the uveitic patients may be useful to follow-up the diagnosed sarcoidosis, as well as for diagnosing sarcoidosis, because the serum KL-6 level was well correlated with the ACE level, and less affected by systemic medication than ACE levels.

Adult↗

Phosphorylation of extracellular signal-regulated kinase and p27(KIP1) after retinal detachment.

PURPOSE: The roles of the extracellular signal-regulated kinase (ERK) pathway in the expression of cyclin D1 and p27(KIP1), the phosphorylation of p27(KIP1), and proliferation activity were examined after retinal detachment. METHODS: Normal eyes and eyes at 15 min, 2 and 4 days after retinal detachment in C57Bl6 mice were examined by immunohistochemistry using anti-phosphorylated (p) ERK1/2, anti-cyclin D1, anti-p27(KIP1), anti-p27(KIP1) phosphorylated at serine 10 (S10-phospho-p27), and anti-proliferating cell nuclear antigen (PCNA) antibodies with or without treatment with a specific ERK inhibitor, PD98059. Mouse Müller cells were isolated and examined for alteration of p27(KIP1) and cyclin D1 after exposure of basic fibroblast growth factor (bFGF) with and without treatment of PD98059 using Western blotting. RESULTS: In the normal retina, nuclear immunoreactivity for p27(KIP1), but not S10-phospho-p27 or pERK1/2, was observed in the middle sublayer of the inner nuclear layer (INL), where Müller glial cells are situated. At 15 min after the retinal detachment, p27(KIP1), S10-phospho-p27 and pERK1/2-positive nuclei were noted in the INL, whereas immunoreactivity for pERK1/2 or S10-phospho-p27 was not observed after treatment with PD98095. Cyclin D1 was induced in the INL 2 days after the retinal detachment, and the induction was inhibited by PD98059. At 4 days after the detachment, p27(KIP1) immunoreactivity was not observed, and cyclin D1 and PCNA were expressed. The disappearance of p27(KIP1) was suppressed, whereas expression of cyclin D1 and PCNA was not observed in mice treated with PD98059. Exposure of bFGF relatively decreased the expression level of p27(KIP1) and increased the level of cyclin D1 in mouse Müller cells, compared with control level. Induction of cyclin D1 and decrease in p27(KIP1) were inhibited with treatment of PD98059. CONCLUSION: Phosphorylation of ERK and expression of p27(KIP1) and cyclin D1 are involved in the proliferation of Müller cells after retinal detachment.

Animals↗

Effects of fucoxanthin on lipopolysaccharide-induced inflammation in vitro and in vivo.

The aim of the present study was to investigate the efficacy of fucoxanthin on endotoxin-induced uveitis (EIU) in rats. The effects of fucoxanthin on endotoxin-induced leucocyte and protein infiltration, nitric oxide (NO), prostaglandin (PG)-E2 and tumour necrosis factor (TNF)-alpha concentrations in rat aqueous humour, as well as on the cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) protein expression in a mouse macrophage cell line (RAW 264.7 cells) were studied. EIU was induced in male Lewis rats by a footpad injection of lipopolysaccharide (LPS). Immediately after the LPS injection, either 0.1, 1 or 10mgkg(-1) of fucoxanthin was injected intravenously. The aqueous humour was collected 24hr later from both eyes, and both the number of cells infiltrating into the aqueous humour and the aqueous humour protein concentration were measured. The levels of PGE2, NO and TNF-alpha were determined by enzyme-linked immunosorbent assay. The RAW 264.7 cells were pretreated with various concentrations of fucoxanthin for 24hr and subsequently incubated with LPS for 24hr. COX-2 and iNOS protein expression was analysed by the Western blotting method. Levels of PGE2, NO and TNF-alpha production were determined. Fucoxanthin suppressed the development of EIU in a dose-dependent fashion. Treatment with fucoxanthin resulted in a reduction in PGE2, NO and TNF-alpha concentrations in the aqueous humour. The expression of COX and iNOS protein in the fucoxanthin treated RAW264.7 cells decreased significantly compared to that the LPS group. It also significantly reduced the concentration of PGE2, NO and TNF-alpha production in the medium of cells. The present result indicate fucoxanthin suppresses the inflammation of EIU by blocking the iNOS and COX-2 protein expression and its anti-inflammatory effect on eye is comparable with the effect of predinisolone used in similar doses.

Animals↗

Retinal neovascularization during treatment with IGF-1 for insulin resistance syndrome.

BACKGROUND: Leprechaunism is a rare congenital syndrome and the most severe form of insulin resistance syndrome, with mutations in the insulin receptor gene. Recombinant human insulin-like growth factor-1 (rhIGF-1) is currently applicable to the treatment for insulin resistance syndrome by its insulin-like effect. Although IGF-1 is thought to promote tissue proliferation and neovascularization, it is uncertain how it acts on the development of diabetic retinopathy. METHODS: Interventional case report. RESULTS: A 12-year-old girl with leprechaunism has been treated with IGF-1 since she was 6 months old. She presented with neovascular glaucoma in the left eye, but with no serious changes in the right fundus except for tortuosity and dilatation of retinal veins. Thereafter, retinal neovascularization in the right eye developed in 6 months to form a loop-shaped vascular network in the vitreous cavity despite panretinal photocoagulation. CONCLUSIONS: Characteristics of retinal neovascularization and clinical course suggest that IGF-1 treatment was closely associated with the development of diabetic retinopathy in this case.

Blindness↗

Comparative study of two sets of criteria for the diagnosis of Vogt-Koyanagi-Harada's disease.

PURPOSE: The Vogt-Koyanagi-Harada's (VKH) Disease Committee established the "Revised diagnostic criteria for VKH disease" in 2001. The purpose of the present study was to assess the concordance between these criteria and the traditional Sugiura's diagnosis system. DESIGN: Observational case series. METHODS: The medical records of patients previously diagnosed with VKH disease based upon Sugiura's criteria at the Uveitis Survey Clinic of the Hokkaido University Hospital between 1991 and 2003 were retrospectively reevaluated using the VKH Committee's revised diagnostic criteria for VKH disease. RESULTS: Sugiura's criteria were used to identify 169 patients with VKH disease. All patients were Japanese, and 95 cases (56%) were women. Mean age at the time of their first visit to our clinic was 44.7 +/- 13.9 years (range, 9 to 74 years). Using the VKH Committee's new criteria, 91.7% of the previously diagnosed VKH patients were classified as having the disease. Of this group, 11.8% were classified as complete, 71% incomplete, and 8.9% as probable VKH disease. CONCLUSIONS: The VKH Committee's revised diagnostic criteria proved useful for VKH disease diagnosis, as the concordance rate for the two criteria was more than 90%. However, patients who had prior cataract surgery or who lacked signs of serous retinal detachment were not classified as having VKH disease because of exclusion by the VKH Committee's new criteria.

Adolescent↗

Clinical features in tubulointerstitial nephritis and uveitis (TINU) syndrome.

PURPOSE: To analyze clinical features of the tubulointerstitial nephritis and uveitis (TINU) syndrome in Japan, especially exacerbations or recurrences of uveitis. DESIGN: Retrospective observational study. METHODS: We reviewed the clinical features in 12 patients with TINU syndrome diagnosed by renal biopsy, who were evaluated and treated at the Department of Ophthalmology, Hokkaido University Hospital. Visual acuity was measured using decimal visual acuity. RESULTS: Patient age ranged from 10 to 33 years (mean 21 years), and females accounted for 83% of the cases. Both eyes were affected in 11 patients (92%). All 12 patients initially experienced ocular symptoms, with hyperemia being the chief complaint. We diagnosed patients as having uveitis and conducted blood tests and urinalysis. Urinalysis did show characteristic findings, most notably glucosuria, increased beta2 microglobulin that were > or = 10 times that of normal levels, and increased N-acetylglucosaminidose levels in a high percentage of patients. Recurrent or exacerbating uveitis was seen in six patients (50%). In exacerbated or recurrent uveitis, inflammation was more severe (> or = 3+ cells of the anterior eye segment). The ocular inflammation generally responded well to treatment with oral corticosteroids, and the number of recurrences was lower at corticosteroid doses of > or = prednisolone 40 mg. CONCLUSIONS: Ophthalmologists play an important role in the initial discovery of patients with TINU syndrome. Because inflammation was more severe in exacerbated or recurrent uveitis, in instances where uveitis is refractory to local therapy, oral corticosteroids should be considered as early as possible.

Administration, Oral↗

Bilateral diffuse uveal melanocytic proliferation in a patient with cancer-associated retinopathy.

PURPOSE: To describe a patient with bilateral diffuse uveal melanocytic proliferation (BDUMP) and cancer-associated retinopathy (CAR). DESIGN: Interventional case report. METHODS: A 66-year-old woman developed progressive vision loss 4 months after total hysterectomy. Ophthalmologic examination, Western blot test of sera and aqueous humor, and immunohistochemistry of carcinoma cells were performed. RESULTS: Testing revealed BDUMP and severe retinal dysfunction. Autoantibodies against recoverin and heat shock cognate protein 70 (hsc 70) were detected in serum. Cytoplasmic immunoreactivity for recoverin and hsc 70 was observed in endometrioid carcinoma cells. CONCLUSIONS: Simultaneous cases of BDUMP and CAR are rare. Aberrantly expressed recoverin and hsc 70 triggered serum autoantibody production, which caused photoreceptor degeneration.

Aged↗

Disappearance of p27(KIP1) and increase in proliferation of the lens cells after extraction of most of the fiber cells of the lens.

PURPOSE: Proliferation of the lens epithelial cells is involved in the fibrotic changes of lens capsules after cataract extraction. However, the mechanisms of the proliferation of the lens epithelial cells are largely unknown. The purpose of this study was to examine the correlation between the expression of p27(KIP1) and cell proliferation in the lens cells after the extraction of lens fiber cells. METHODS: At embryonic days (E) 14 and 18, the C57Bl6 mice were anesthetized and the embryos were surgically removed. The eyes were dissected from these embryos and also from mice 12 weeks after birth. The 12-week-old mice were anesthetized, and then the lens fiber cells were extracted. Normal eyes at E14 and 18 and eyes fixed at 15 min and 48 hr after the extraction of the lens fiber cells were analyzed using immunohistochemistry with anti-p27(KIP1), p57(KIP2), and phosphorylated extracellular signal-regulated kinase (phospho-ERK) 1/2 antibodies, and cells in the S phase of the cell cycle were also examined using anti-bromodeoxyuridine (BrdU) antibody. RESULTS: p27(KIP1) and p57(KIP2)-positive cells were present in the equatorial region of E14 mice. At E18, many lens fiber cells showed nuclear immunoreactivity for p27(KIP1), whereas a small number of cells were positive for p57(KIP2) in the equatorial region. At 12 weeks of age, all nuclei of the lens epithelial cells as well as lens fiber cells showed nuclear immunoreactivity for p27(KIP1). In contrast, p57(KIP2) and phospho-ERK1/2 were not expressed in the lens cells. At 15 min after the extraction of lens fiber cells, phospho-ERK1/2 as well as p27(KIP1) were detected in the lens cells. At 48 hr after the extraction of the lens fiber cells, a few p27(KIP1)-positive nuclei were observed in the equatorial region of the lens capsule. In contrast, many lens cells showed nuclear immunoreactivity for BrdU. CONCLUSIONS: These findings suggest that degradation of p27(KIP1) mediated by phosphorylation of ERK 1/2 is correlated with proliferation of the epithelial cells after the extraction of the lens fiber cells.

Animals↗

Tolerability and efficacy of N-chlorotaurine in epidemic keratoconjunctivitis--a double-blind, randomized, phase-2 clinical trial.

The aim of this study was to assess the tolerability and efficacy of N-chlorotaurine (NCT), an endogenous antimicrobial agent, in epidemic keratoconjunctivitis. In a prospective double-blind, randomized phase 2b study, the infected eyes were treated for 7 days with eye drops containing 1% aqueous solution of N-chlorotaurine (33 subjects) or gentamicin (27 subjects, control group). Adenovirus types 3, 4, 8, 19, and 37 were detected in 39 subjects (65%), enteroviruses in 8 (13.3%), and staphylococci in 5 (8.3%). Subjective and objective symptoms were scaled and added to a subjective and objective score, respectively, on day 1 (baseline), day 4, and day 8. Analyzing the whole study population, the subjective score on day 8 was lower in the NCT group (P = 0.016), whereas there were no differences in the objective score. However, in severe infections caused by adenovirus type 8 (n = 20) both the subjective and objective score were lower in the NCT group on day 4 (P = 0.003 and 0.015, respectively), which was also true for the subjective score on day 8 (P = 0.004) in this subgroup. The frequency of subepithelial infiltrates was similar in both groups. N-chlorotaurine was well-tolerated, shortened the duration of illness, and seems to be a useful causative therapeutic approach in severe epidemic keratoconjunctivitis.

Adenoviridae↗

The effects of naringin and naringenin on endotoxin-induced uveitis in rats.

The aim of this study was to investigate the efficacy of naringin and naringenin on endotoxin- induced uveitis (EIU) in rats. EIU was induced in male Lewis rats by a footpad injection of lipopolysaccharide (LPS). The rats were injected intravenously with 0.4, 4, or 40 microg/kg naringin or naringenin. Each compound was administered three times, simultaneously, 30 min before and after the actual LPS injection. The aqueous humor was collected 24 h later from both eyes, and the number of cells infiltrating into the aqueous humor and the aqueous humor protein concentration were measured. The levels of prostaglandin E2 (PGE2) and nitric oxide (NO) were determined. Naringin and naringenin suppressed the development of EIU in a dose-dependent fashion. Both treatments with naringin and naringenin produced reductions in PGE2 and NO concentrations in the aqueous humor. In particular, 40 microM/kg of naringin and naringenin suppressed increases in cell count owing to LPS treatment by 31% and 38%, respectively. The possible mechanism for the antiocular inflammatory effect may be the suppression of PGE2 and NO by naringin and naringenin.

Animals↗