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Biomedical subjects

Kazuo Tsubota

Publications and source records attributed to Kazuo Tsubota.

At least 55 records · Page 3Linked to original sources
PubMed2006

Neuroprotective effects of angiotensin II type 1 receptor (AT1R) blocker, telmisartan, via modulating AT1R and AT2R signaling in retinal inflammation.

PURPOSE: To investigate the retinal neural damage that occurs during inflammation and the therapeutic effects of the angiotensin II type 1 receptor (AT1R) blocker, telmisartan, using a model of endotoxin-induced uveitis (EIU). METHODS: The localization of AT1R and AT2R was shown by immunohistochemistry. EIU was induced by intraperitoneal injection of lipopolysaccharide (LPS). Animals were treated with telmisartan for 2 days and were evaluated 24 hours later. Expression levels of angiotensin II, STAT3 activation induced by inflammatory cytokines, and retinal proteins essential for neural activities (e.g., synaptophysin, rhodopsin) were analyzed by immunoblot. An AT2R antagonist was administered to evaluate the contribution of AT2R signaling in this therapy. Dark-adapted full-field electroretinography (ERG) was also performed. RESULTS: AT1R and AT2R were expressed in presynaptic terminals in most of the retinal neurons. AT1R was also expressed in Müller glial cells. During inflammation, angiotensin II expression was elevated, STAT3 was activated, and synaptophysin and rhodopsin expression were reduced. The expression of glial fibrillary acidic protein (GFAP), downstream of STAT3 activation, was induced in Müller glial cells. However, treatment with telmisartan successfully avoided all these changes. An AT2R antagonist lowered synaptophysin expression despite the treatment. STAT3 activity was negatively correlated with rhodopsin expression. Furthermore, ERG responses, which were mostly prevented by telmisartan, were disturbed during inflammation. CONCLUSIONS: Retinal protein expression and visual function are both disturbed by inflammation. Treatment with the AT1R blocker telmisartan efficiently prevented these signs of retinal neural damage through the reduction of local angiotensin II expression, the blockade of AT1R, and the relative upregulation of AT2R function.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2006

Cytokeratin 15 can be used to identify the limbal phenotype in normal and diseased ocular surfaces.

PURPOSE: To elucidate the expression pattern of K15, K19, K14, and K12 in human and mouse ocular surface epithelium as putative markers of epithelial phenotype. METHODS: Immunohistochemical staining with specific antibodies for K15, K19, K14, and K12 was performed in human donor cornea tissue and normal ICR mouse corneas, with emphasis on localization of immunopositive cells. Immunohistochemistry was performed in a limbus-deficient mouse model as well as in clinical samples of pannus surgically removed from a thermal burn and a patient with Saltzmann's dystrophy. Staining patterns were classified as limited to the most basal layer (K(bas)), basal and suprabasal layers (K(bas-sup)), predominantly in suprabasal layers (K(sup)) and negative staining (K(-)). RESULTS: In human conjunctival epithelium, strong expression of K15 was observed in basal cells, whereas K19 was expressed in both basal and suprabasal layers (K15(bas)/K19(bas-sup)/K12(-)). Limbal epithelial cells were K15(bas-sup)/K19(bas-sup)/K12(sup), whereas epithelial cells in the central cornea were K15(-)/K19(bas-sup)/K12(bas-sup). In contrast, the mouse ocular surface demonstrated a different expression pattern of K15 and K19 than did the human tissue in the conjunctiva (K15(bas-sup)/K19(bas)/K12(-)) and the limbus (K15(bas-sup)/K19(bas)/K12(sup)). Neither K15 nor K19 was expressed in the central mouse cornea (K15(-)/K19(-)/K12(bas-sup)). Similar cytokeratin expression was observed in conjunctivalized corneas in mice and in surgically removed pannus tissue. CONCLUSIONS: Although the expression of K15 and K19 differ in humans and mice, specific staining patterns can be used to characterize the epithelial phenotype in normal and diseased ocular surface.

Animals↗
PubMed2006

Traumatic epithelial flap detachment after laser subepithelial keratomileusis.

PURPOSE: To report a case of corneal epithelial flap detachment 20 days after laser subepithelial keratomileusis (LASEK). METHODS: A 30-year-old man underwent LASEK for correction of myopia. On postoperative day 8, he was comfortable and the corneal epithelium healed completely with uncorrected visual acuity (UCVA) of 20/20. On postoperative day 20, the corneal epithelial flap on the right eye detached and was lost during pressure patching after puncture of the hordeolum. RESULTS: The corneal defect was treated with a bandage contact lens, levofloxacin, and hyaluronic acid eye drops. Ten days after detachment, UCVA had improved to 20/20 and the epithelium had closed completely. CONCLUSIONS: Mild trauma can cause epithelial flap detachment during the early postoperative period of LASEK.

Adult↗
PubMed2006

Dry eye after LASIK enhancement by flap lifting.

PURPOSE: To determine whether dry eye after LASIK recurs after LASIK enhancement. METHODS: A total of 63 eyes of 42 patients who underwent LASIK enhancement were included in this study. Subjective dry eye symptoms, tear break-up time (BUT), Schirmer test with anesthesia, fluorescein staining of the cornea, and corneal sensitivity were evaluated before and at 1, 3, and 6 months after enhancement. RESULTS: The subjective dry eye symptoms remained unchanged before and after LASIK enhancement. Similarly, Schirmer values and tear BUT did not exhibit statistically significant differences between the pre- and post-enhancement values. Compared with the pre-enhancement values, the fluorescein score was higher at 1 month after surgery and further improved at 3 months. In comparison with the pre-enhancement values, the corneal sensitivity was decreased at 1, 3, and 6 months after surgery. CONCLUSIONS: Patients did not complain of dry eye symptoms and tear functions were not compromised after LASIK enhancement. These results suggest that factors other than the neurotrophic effect may contribute to dry eye after LASIK.

Adult↗
PubMed2006

Comparison of LASIK using the NIDEK EC-5000 optimized aspheric transition zone (OATz) and conventional ablation profile.

PURPOSE: To compare a new ablation algorithm termed the optimized aspheric transition zone (OATz) with the conventional laser ablation profile for correction of myopic astigmatism. METHODS: LASIK using OATz profile #6 or using conventional ablation profile was performed on 98 eyes of 53 patients (OATz #6 group) and 111 eyes of 66 patients (control #6 group), respectively. Further, LASIK using OATz profile #5 or using the conventional ablation profile was performed on 109 eyes of 58 patients (OATz #5 group) and 109 eyes of 75 patients (control #5 group), respectively. The effective optical zone, uncorrected visual acuity, manifest refraction, aberrations, contrast sensitivity, and patient satisfaction at 3 months postoperatively were compared between the OATz #6 and control #6 groups and between the OATz #5 and control #5 groups. RESULTS: The effective optical zones in the OATz #6 group (6.45 +/- 0.29 mm) or OATz #5 group (6.40 +/- 0.21 mm) were significantly larger than those in the control #6 group (6.33 +/- 0.27 mm) or control #5 group (6.26 +/- 0.25 mm) (P < .01), respectively. Uncorrected visual acuity and manifest refraction were similar in all groups. The changes in contrast sensitivity were significant and favored the OATz #6 (P < .01) and OATz #5 groups (P < .05). The patient satisfaction survey found no statistical difference at 3 months postoperatively. CONCLUSIONS: Patients treated with the OATz profiles had better visual quality as measured by contrast sensitivity and also had larger effective optical zones as compared with those treated by the conventional ablation profile.

Adult↗
PubMed2006

Fourier analysis of single running suture adjustment in penetrating and deep lamellar keratoplasty.

PURPOSE: To prospectively evaluate clinical and visual results of running suture adjustment after keratoplasty. METHODS: Thirty-seven eyes of 33 patients received running suture adjustment after keratoplasty. Changes in uncorrected visual acuity, distance best spectacle-corrected visual acuity (BSCVA), refraction, and Fourier analysis constituents were assessed before and after suture adjustment. RESULTS: Thirty eyes, which had improvement of distance BSCVA soon after suture adjustment, maintained improvement at 1 year, whereas 7 eyes with decreased distance BSCVA soon after suture adjustment experienced no improvement at 1 year. Patients with poor distance BSCVA at 1 year had significantly higher high order irregularity than patients with better distance BSCVA despite similar cylindrical power outcomes.

Adult↗
PubMed2005

[Quantitative tear study using the red phenol test in the Brazilian population].

PURPOSE: To detect normal values of red phenol thread test in the Brazilian population and compare it between different races, age and sex. METHODS: 280 white individuals (560 eyes) and 280 non-white individuals (560 eyes) were analyzed regarding sex and age, and analyzed using the Phenol Red test. Individuals with ocular diseases, contact lens or ocular drug users were excluded from this study. RESULTS: Of the 1,120 evaluated eyes, the mean +/- standard deviation result was 19.77+/-7.90 mm. CONCLUSIONS: The mean result found in this study was an intermediate value compared to the previously studied populations (Japanese and American).

Adolescent↗
PubMed2005

Critical role of the fifth domain of E-cadherin for heterophilic adhesion with alpha E beta 7, but not for homophilic adhesion.

The integrin alpha(E)beta(7) is expressed on intestinal intraepithelial T lymphocytes and CD8(+) T lymphocytes in inflammatory lesions near epithelial cells. Adhesion between alpha(E)beta(7)(+) T and epithelial cells is mediated by the adhesive interaction of alpha(E)beta(7) and E-cadherin; this interaction plays a key role in the damage of target epithelia. To explore the structure-function relationship of the heterophilic adhesive interaction between E-cadherin and alpha(E)beta(7), we performed cell aggregation assays using L cells transfected with an extracellular domain-deletion mutant of E-cadherin. In homophilic adhesion assays, L cells transfected with wild-type or a domain 5-deficient mutant formed aggregates, whereas transfectants with domain 1-, 2-, 3-, or 4-deficient mutants did not. These results indicate that not only domain 1, but domains 2, 3, and 4 are involved in homophilic adhesion. When alpha(E)beta(7)(+) K562 cells were incubated with L cells expressing the wild type, 23% of the resulting cell aggregates consisted of alpha(E)beta(7)(+) K562 cells. In contrast, the binding of alpha(E)beta(7)(+) K562 cells to L cells expressing a domain 5-deficient mutant was significantly decreased, with alpha(E)beta(7)(+) K562 cells accounting for only 4% of the cell aggregates, while homophilic adhesion was completely preserved. These results suggest that domain 5 is involved in heterophilic adhesion with alpha(E)beta(7), but not in homophilic adhesion, leading to the hypothesis that the fifth domain of E-cadherin may play a critical role in the regulation of heterophilic adhesion to alpha(E)beta(7) and may be a potential target for treatments altering the adhesion of alpha(E)beta(7)(+) T cells to epithelial cells in inflammatory epithelial diseases.

Animals↗
PubMed2005

Massive bilateral vitreoretinal hemorrhage in patient with chronic refractory idiopathic thrombocytopenic purpura.

BACKGROUND: We describe a patient with chronic, refractory idiopathic thrombocytopenic purpura (ITP) who developed massive vitreoretinal hemorrhages in both eyes. METHODS: A 49-year-old woman complained of an acute decrease of vision, and ophthalmoscopy revealed bilateral preretinal and subretinal hemorrhages around the optic disc. Her platelet counts were less than 5000/mul in spite of repetitive administration of corticosteroids and immunoglobulins with splenectomy for the chronic refractory ITP. One month later, she developed massive vitreoretinal hemorrhages bilaterally, and vision decreased to hand-motion. RESULTS: Vitrectomy was performed on both eyes after medical treatment to increase platelet counts. The intraretinal hemorrhages were absorbed from the area around the disc and vision recovered to 20/100 in the right eye and 20/2000 in the left after one month. CONCLUSION: Massive vitreoretinal hemorrhages can develop in patients with chronic refractory ITP, and vitrectomy can be beneficial for this condition.

Chronic Disease↗
PubMed2005

The effect of autologous serum eyedrops in the treatment of severe dry eye disease: a prospective randomized case-control study.

PURPOSE: To evaluate the effectiveness of the autologous serum eyedrops in the treatment of severe dry eye patients. DESIGN: Prospective randomized case-control study. METHODS: Thirty-seven eyes of twenty severe dry eye patients without punctal occlusion were enrolled in this study. After 2 weeks of washout, they were randomly assigned to two groups. Group A patients used only preservative-free artificial tears, and group S patients used only autologous serum eyedrops. We evaluated the results of Schirmer test, fluorescein and rose bengal staining scores, tear film breakup time (BUT), and subjective symptom scores before and 2 weeks after treatment. RESULTS: Mean BUT and fluorescein and rose bengal staining scores, as well as subjective symptom scores, showed significant improvement in the patients assigned to autologous serum eyedrops compared with subjects assigned to preservative-free artificial tears after 2 weeks of treatment. CONCLUSIONS: Autologous serum eyedrops were found effective in the treatment of severe dry eye disease, as evidenced by improvement of tear stability and ocular surface vital staining scores.

Aged↗
PubMed2005

The application of a new continuous functional visual acuity measurement system in dry eye syndromes.

PURPOSE: To evaluate the efficacy of a new continuous functional visual acuity measurement (FVAM) system for the assessment of dry eye patients. DESIGN: Prospective comparative study. METHODS: Monocular recognition acuity measured continuously by the FVAM system during a 30-second blink-free period was defined as functional visual acuity (FVA). Examinations using the FVAM system were conducted in 35 eyes of 20 healthy controls and 19 eyes of 13 dry eye patients. Tear function examinations including the Schirmer test, tear film break-up time, and fluorescein and Rose Bengal staining were performed in all subjects. Functional visual acuity and tear functions were also examined before and after insertion of punctum plugs in dry eye patients. Functional visual acuity results at 10, 20, and 30 seconds were compared. RESULTS: Functional visual acuity in dry eyes were significantly lower than control subjects at all time points (P < .05). Functional visual acuity after punctum plugs insertion improved significantly at all time points (P < .05). CONCLUSIONS: FVAM system seemed not only to be an effective tool in the assessment of dynamic visual acuity changes in dry eye and normal subjects but in evaluating the outcome of management of dry eye disease by punctum plugs.

Adult↗
PubMed2005

Clinical evaluation of the accuracy of intraocular pressure measurement by Tono-Pen XL in eyes with amniotic membrane patching.

PURPOSE: To evaluate the influence of amniotic membrane on intraocular pressure (IOP) measurement with the Tono-Pen. DESIGN: Observational case series. METHOD: Eight patients with partial limbal dysfunction who underwent penetrating keratoplasty were recruited. Amniotic membranes were patched just after keratoplasty. One week postoperatively, amniotic membranes were removed, and accuracy of IOP measurement with the Tono-Pen was evaluated with comparisons before and after the removal. RESULTS: No epithelial defects were detected after the removal of amniotic membrane. Mean IOPs with and without amniotic membranes were 16.6 +/- 3.0 mm Hg (mean +/- SD) and 16.0 +/- 3.7 mm Hg, respectively. The difference was not statistically significant. CONCLUSIONS: Assessment of IOP with the Tono-Pen was observed to be accurate even when used over an amniotic membranes patch in cases who underwent penetrating keratoplasty.

Adult↗
PubMed2005

Electrolysis for corneal opacities in a young patient with superficial variant of granular corneal dystrophy (Reis-Bücklers corneal dystrophy).

PURPOSE: To report the efficacy of electrolysis as a treatment of corneal opacities in a young patient with the superficial variant of granular corneal dystrophy. DESIGN: Interventional case report. METHODS: An 11-year-old boy presented with subepithelial opacities in both eyes. His visual acuity was 0.2 in the left eye; he received corneal electrolysis under topical anesthesia. RESULTS: The electrolysis, which required only 5 minutes, resulted in the disappearance of the subepithelial opacities. His visual acuity improved to 0.4 on the next day and was 1.0 eight months later. The corneal curvature and thickness were not altered by the electrolysis. CONCLUSIONS: Corneal electrolysis proved to be an effective treatment for subepithelial opacities, and we recommend electrolysis as an effective and simple treatment for young patients with SGCD.

Child↗
PubMed2005

TGF-beta1, IL-1beta, and Th2 cytokines stimulate vascular endothelial growth factor production from conjunctival fibroblasts.

Giant papillary formation containing newly formed vessels is a major characteristic of severe allergic conjunctivitis, such as atopic keratoconjunctivitis (AKC) or vernal keratoconjunctivitis (VKC). We examined production of vascular endothelial growth factor (VEGF) from cultured conjunctival fibroblasts from normal volunteers under stimulation with type 1-, type 2-helper T cell derived and proinflammatory cytokines to investigate the mechanism of giant papillae formation in AKC/VKC. Primary cultured conjunctival fibroblasts were incubated with interleukin (IL)-4, IL-13, IL-1beta, IL-2, tumor necrotizing factor (TNF)-alpha, interferon (IFN)-gamma, or transforming growth factor (TGF)-beta1. Effects of cytokines on VEGF protein secretion in supernatant were assessed by ELISA, and VEGF mRNA expression in cultured cells were assessed by quantitative PCR. TGF-beta1 most effectively increased VEGF concentration with dose- and time-dependent manner IL-1beta, IL-4, and IL-13 significantly increased VEGF concentration. Though IL-2 also showed slight increase of VEGF concentration, it was not statistically significant. TNF-alpha and INF-gamma did not increase VEGF concentration. Quantitative PCR showed significant increase of VEGF mRNA in TGF-beta1, IL-1beta, and IL-4 stimulated fibroblasts. TGF-beta1, IL-1beta, and Th2 cytokines from allergic inflammatory cells induced VEGF production in conjunctival fibroblasts, and may play a crucial role in neovascularization and formation of giant papillae in AKC/VKC.

Cell Division↗
PubMed2005

Melanocytes in the corneal limbus interact with K19-positive basal epithelial cells.

The human corneal limbus is identified by the distinct features of the palisades of Vogt (POV), which contain pigment granules that are aligned with the microplicae of the epithelium. Although it is presumed that pigments are produced by melanocytes, the characterization of melanocytes in the limbus has not been clearly documented. We examined human limbal tissues by whole mounts and serial histological sections to localize epithelial cells containing melanin granules. Most of the pigmented cells observed by immunohistochemistry were K19 (+) cells in the basal limbal epithelium. A superimposed image revealed that melanin granules were oriented towards the apex of each K19 (+) cell, acting as a pigmented cap facing the ocular surface. Melanocytes were identified by MART1, an antigen specific to melanocyte-lineage cells. Melanocytes were shown to exist as sporadic cells with dendritic processes that extend to surrounding epithelial cells. Melanocytes were also found in light-pigmented donor tissue when visualized by the tyrosinase assay using the enzyme substrate DOPA. Since tyrosinase activity was not found in epithelial cells, the production of melanin is exclusively the role of melanocytes that comprised 5.3+/-2.7% of the total cells in cytospin samples (N=3). Melanocytes and K19 (+) epithelial cells may form a functional network similar to the melanin unit of the skin.

Aged↗
PubMed2005

Experience with the Artisan phakic intraocular lens in Asian eyes.

PURPOSE: To investigate the efficacy and safety of implantation of an iris-claw phakic intraocular lens (PIOL), Artisan Myopia, in Asian eyes. SETTING: Minamiaoyama Eye Clinic, Tokyo, Japan. METHODS: Forty-four eyes of 32 Japanese patients and 1 Korean patient with high myopia had Artisan Myopia lens implantation to correct their refractive errors. Lens models, 5/8.5 or 6/8.5 (optic diameter/overall diameter), were chosen as standard lens model. A smaller lens model (5/7.5-Artisan Myopia Small) was implanted in eyes with corneal diameter less than 11.0 mm. Postoperative examinations were performed on 1 day, 1 week, 1 month, 3 months, 6 months, 1 year, and 2 years after surgery. Uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), manifest refraction, corneal endothelial cell counts, intraocular pressure, and complications were evaluated. RESULTS: Artisan Myopia Small lenses were implanted in 4 eyes (9.1%) and 8.5 mm diameter lenses were implanted in 40 eyes. Preoperative UCVA (logMAR) improved from 1.57 to 0.09 at 1 month after surgery and no regression was observed thereafter. Postoperative manifest refraction was -1.02 +/- 0.87 D (-3.25 to -0.00 D), and within 1.0 D in 20 eyes (55.6%), within 2.0 D in 32 eyes (88.9%) at 1 month after surgery, and stable during the follow-up period. The final BCVA decreased 2 lines in 2 eyes (4.5%) due to progression of age-related cataract. No serious complications such as angle closure or progressive endothelial cell loss were observed. CONCLUSION: Implantation of an Artisan iris-claw PIOL implantation may be a safe and effective procedure for Asian eyes.

Adult↗