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Biomedical subjects

Yasuo Tano

Publications and source records attributed to Yasuo Tano.

At least 91 records · Page 5Linked to original sources

Otx2 homeobox gene controls retinal photoreceptor cell fate and pineal gland development.

Understanding the molecular mechanisms by which distinct cell fate is determined during organogenesis is a central issue in development and disease. Here, using conditional gene ablation in mice, we show that the transcription factor Otx2 is essential for retinal photoreceptor cell fate determination and development of the pineal gland. Otx2-deficiency converted differentiating photoreceptor cells to amacrine-like neurons and led to a total lack of pinealocytes in the pineal gland. We also found that Otx2 transactivates the cone-rod homeobox gene Crx, which is required for terminal differentiation and maintenance of photoreceptor cells. Furthermore, retroviral gene transfer of Otx2 steers retinal progenitor cells toward becoming photoreceptors. Thus, Otx2 is a key regulatory gene for the cell fate determination of retinal photoreceptor cells. Our results reveal the key molecular steps required for photoreceptor cell-fate determination and pinealocyte development.

Animals↗

Nuclear cataract caused by a lack of DNA degradation in the mouse eye lens.

The eye lens is composed of fibre cells, which develop from the epithelial cells on the anterior surface of the lens. Differentiation into a lens fibre cell is accompanied by changes in cell shape, the expression of crystallins and the degradation of cellular organelles. The loss of organelles is believed to ensure the transparency of the lens, but the molecular mechanism behind this process is not known. Here we show that DLAD ('DNase II-like acid DNase', also called DNase IIbeta) is expressed in human and murine lens cells, and that mice deficient in the DLAD gene are incapable of degrading DNA during lens cell differentiation--the undigested DNA accumulates in the fibre cells. The DLAD-/- mice develop cataracts of the nucleus lentis, and their response to light on electroretinograms is severely reduced. These results indicate that DLAD is responsible for the degradation of nuclear DNA during lens cell differentiation, and that if DNA is left undigested in the lens, it causes cataracts of the nucleus lentis, blocking the light path.

Animals↗

Sub-retinal hemorrhage during internal limiting membrane peeling for a macular hole.

PURPOSE: To report the occurrence of sub-retinal hemorrhage during peeling of the internal limiting membrane (ILM). CASE REPORTS: In case 1, a three-port pars plana vitrectomy was performed on a 57-year-old woman with a macular hole. Following the staining of the ILM with indocyanine green, the ILM was peeled with forceps, and a sub-retinal and vitreous hemorrhage resulted from a vein during the peeling. The bleeding was stopped by elevating the intraocular pressure. The final visual acuity was 20/30. In case 2, similar procedures were performed on a 68-year-old woman with a macular hole. A sub-retinal hemorrhage occurred while peeling the ILM. The pre-operative visual acuity was 20/300, and final visual acuity was 20/200. CONCLUSIONS: Surgeons should be aware that sub-retinal and vitreous hemorrhage can be a complication of ILM peeling.

Aged↗

Protective effect of nilvadipine against glutamate neurotoxicity in purified retinal ganglion cells.

We determined the effect of nilvadipine, a dihydropyridine-type calcium channel blocker, in preventing glutamate neurotoxicity in purified retinal ganglion cells (RGCs). RGCs were purified from dissociated rat retinal cells (postnatal days 6-8), using a modified two-step panning method, and cultured in serum-free medium containing neurotrophic factors and forskolin. RGC survival after exposure to glutamate (25 microM) with nilvadipine or other calcium channel blockers was measured by calcein-acetoxymethyl ester staining after 3 days in culture. Changes in the level of intracellular Ca(2+) ([Ca(2+)](i)) were measured with fura-2 fluorescence. Induction of apoptosis was evaluated using the TDT-dUTP terminal nick-end labeling technique. The neurotoxic effects of low doses of glutamate were blocked by a specific alpha-amino-3-dihydro-5-methylisoxazole-4-propionate-kainate receptor antagonist, 6,7-dinitroquinoxaline-2,3-dione (20 microM). Simultaneous application of nilvadipine (1-100 nM) with glutamate protected against glutamate neurotoxicity in a dose-dependent manner. Calcium-imaging experiments showed that the glutamate-evoked [Ca(2+)](i) increase was significantly blocked by nilvadipine (P<0.001), but not nifedipine and diltiazem, in about 50% of RGCs. In addition, the application of nilvadipine significantly reduced glutamate-induced apoptosis (P<0.001). These findings suggest that nilvadipine may partly inhibit glutamate-induced apoptotic cell death by blocking calcium influx via voltage-dependent calcium channels in purified RGCs.

Animals↗

Synaptic targeting of PSD-Zip45 (Homer 1c) and its involvement in the synaptic accumulation of F-actin.

PSD-Zip45/Homer1c, which contains an enabled/VASP homology 1 (EVH1) domain and leucine zipper motifs, is a postsynaptic density (PSD) scaffold protein that interacts with metabotropic glutamate receptors and the shank family. We studied the molecular mechanism underlying the synaptic targeting of PSD-Zip45 in cultured hippocampal neurons. The EVH1 domain and the extreme C-terminal leucine zipper motif were molecular determinants for its synaptic targeting. The overexpression of the mutant of the EVH1 domain or deletion of the extreme C-terminal leucine zipper motif markedly suppressed the synaptic localization of endogenous shank but not PSD-95 or GKAP. In contrast, an overexpressed GKAP mutant lacking shank binding activity had no effect on the synaptic localization of shank. Actin depolymerization by latrunculin A reduced the synaptic localization of PSD-Zip45, shank, and F-actin but not of PSD-95 or GKAP. Overexpression of PSD-Zip45 enhanced the accumulation of synaptic F-actin. Additionally, overexpression of PSD-Zip45 and an isoform of shank induced synaptic enlargement in association with the further accumulation of synaptic F-actin. The EVH1 domain and extreme C-terminal leucine zipper motif of PSD-Zip45 were also critical for these events. Thus, these data suggest that the PSD-Zip45-shank and PSD-95-GKAP complexes form different synaptic compartments, and PSD-Zip45 alone or PSD-Zip45-shank is involved in the synaptic accumulation of F-actin.

Actins↗

Experimental study of viscoelastic in the prevention of corneal endothelial desiccation injury from vitreal fluid-air exchange.

PURPOSE: To evaluate the usefulness of viscoelastic in protecting the corneal endothelium from desiccation injury associated with fluid-air exchange in a rabbit model. DESIGN: Experimental study. METHODS: Rabbit eyes undergoing pars plana lensectomy and vitrectomy were insufflated with either dry or humidified air for 20 minutes following introduction of either Opegan (sodium hyaluronate 1.0%; Santen, Osaka, Japan) or Viscoat (sodium hyaluronate 3%-chondroitin sulfate 4%; Alcon, Tokyo, Japan) into the anterior chamber. In two other groups of rabbit eyes, the same procedure was performed without using any viscoelastic agent. Corneas obtained from rabbits undergoing surgery were compared with corneas obtained from rabbits not undergoing surgery. Potential alterations in the corneal endothelium were investigated by scanning electron microscopy, by Phalloidin-FITC staining of actin and by in vitro measurements of corneal permeability for carboxyfluorescein using a diffusion chamber. RESULTS: Scanning electron microscopy displayed less distortion of corneal endothelium with Opegan and Viscoat compared with the dry air-only exposed corneas. Using humidified air in Opegan and Viscoat coated corneas maintained the normal actin cytoskeleton during fluid-air exchange. Paracellular leakage was much less with Opegan and Viscoat use following infusion of dry air comparing to that of dry air-only group (P =.026 and P =.041). The difference was much more striking following humidified air infusion in Opegan or Viscoat coated corneas comparing to dry air-only infused corneas (P <.002 and P <.002). CONCLUSIONS: Coating of rabbit corneal endothelium with Opegan or Viscoat before fluid-air exchange largely prevents dry air damage to the endothelium. Infusion of humidified air further protects corneal endothelium during fluid-air exchange in aphakic rabbit eyes.

Actins↗

Modified technique to create retinal detachment during macular translocation surgery.

PURPOSE: To report a modified technique for creating total retinal detachment during macular translocation surgery with a 360-degree retinotomy. DESIGN: Interventional case series. METHODS: After vitrectomy, BSS Plus (Alcon, Fort Worth, TX, USA) was injected into the subretinal space with a 39-gauge needle to create a small retinal detachment. The tip of a 20-gauge silicone-tipped needle was then placed in the hole created by the needle, and BSS Plus was injected subretinally at a high flow rate. RESULTS: In 10 eyes (10 patients), we created one iatrogenic retinal hole in seven eyes and two holes in three eyes. The time needed to create total retinal detachment was decreased. CONCLUSIONS: Our technique seems to make creation of a total retinal detachment easier compared with the previous standard procedure and may reduce postoperative complications following macular translocation surgery with a 360-degree retinotomy.

Bicarbonates↗

Continuous outflow devices for macular translocation with 360-degree retinotomy.

PURPOSE: Separation of the retina from retinal pigment epithelium is the most difficult step in macular translocation surgery. To complete this critical step, we have developed two specially designed continuous outflow needles, a rigid needle for creating retinal detachment and a liquid perfluorocarbon injection needle with a soft tip. DESIGN: Experimental study, new instrument development. METHODS: To permit continuous outflow during separation of the retina from the retinal pigment epithelium, the shaft of the continuous outflow needle is smaller than 20 gauge in diameter to allow continuous flow of fluid from the vitreous cavity. RESULTS: These instruments have been used successfully in 54 eyes that underwent macular translocation with 360-degree retinotomy. The rigid needle creates safe retinal detachment by keeping intraocular pressure lower, which is strictly needed for this step. The injection needle facilitates injection of perfluorocarbon liquid while manipulating the retina gently with its soft tip. CONCLUSION: Continuous outflow instruments are useful tools because they facilitate critical steps in the delicate process of macular translocation surgery.

Choroidal Neovascularization↗

Sclerotic scattering illumination during phototherapeutic keratectomy for better visualization of corneal opacities.

PURPOSE: To report on a simple method to obtain a better view of corneal opacities during excimer laser phototherapeutic keratectomy (PTK). DESIGN: An interventional case report. METHODS: Phototherapeutic keratectomy was performed under sclerotic scattering illumination with a vitrectomy-endoilluminator at the limbus. RESULTS: During conventional PTK with diffuse illumination, the intraoperative observations of corneal opacities are not as good as that with a slit lamp. Conversely, subtle corneal opacities can be easily seen with sclerotic scattering illumination even under a surgical microscope. CONCLUSIONS: The use of sclerotic scattering illumination during PTK is valuable, because it provides a better view of opacified tissues and avoids excessive ablation.

Corneal Opacity↗

Frequency of epithelial debridement during diabetic vitrectomy.

PURPOSE: To survey active vitreoretinal surgeons to determine how often they intentionally debride the corneal epithelium during vitrectomy surgery for diabetic patients and to ascertain whether the selection of the surgical lens type influences the debridement rate. DESIGN: Observational retrospective case series. METHODS: Fifty-five vitreoretinal surgeons were asked to retrospectively report how many pars plana vitrectomies they performed in 1 year on diabetic eyes and in what percent of the cases was debridement of the cornea necessary. In a second query, they were asked to note which specific type of surgical lens system (hand-held irrigating, Landers sew-on, or Oculus BIOM noncontact) was used for their surgical intervention. RESULTS: The total number of diabetic vitrectomies performed in 1 year by the respondents was 8,002. The frequency of epithelial debridement was 17.4%, with a range of 0% to 90%. The use of irrigating contact lenses was associated with a significantly higher rate of debridement compared with the use of sew-on or BIOM noncontact lenses (23.5% vs 12.1%, P <.001). Regarding the 41 surgeons who indicated a specific type of lens used, we found that the debridement rate for infusion lenses was 23.8% compared with 13.0% for sew-on lenses and 15.6% for noncontact BIOM lenses. The difference between these groups was statistically significant (P <.025). CONCLUSIONS: Irrigating contact lenses appear to increase the need for epithelial debridement compared with other alternatives. Sew-on lenses with a viscoelastic cushion may provide the best corneal protection.

Debridement↗

Optical coherence tomographic evaluation of a surgically treated traumatic macular hole secondary to Nd:YAG laser injury.

PURPOSE: To report the importance of optical coherence tomographic (OCT) evaluation of a macular hole caused by neodymium:yttrium-aluminum-garnet (Nd:YAG) laser injury. DESIGN: Observational case report. METHODS: A 33-year-old man presented with an accidental Nd:YAG laser-induced macular hole in his right eye. After observing the course of the macular hole by OCT, the macular hole was treated by standard pars plana vitrectomy. The appearance of the macular hole was also followed up postoperatively. RESULTS: Seven days after the injury, OCT showed a full-thickness macular hole without a fluid-cuff or swelling of the surrounding retina. Twenty-one days after the injury, however, OCT disclosed that the retina around the macular hole was swollen. After vitrectomy, OCT showed that the macular hole was closed, and the visual acuity improved from 20/30 to 20/20. CONCLUSIONS: Surgical treatment can improve the visual function of eyes with a Nd:YAG laser-induced macular hole. Optical coherence tomography is valuable in providing precise information about the condition of the macula.

Adult↗

Successful photodynamic therapy with verteporfin for recurrent choroidal neovascularization beneath the new fovea after macular translocation surgery with 360-degree retinotomy.

PURPOSE: To report a case of successfully treated recurrent choroidal neovascularization after macular translocation surgery with 360-degree retinotomy by photodynamic therapy with verteporfin. DESIGN: Interventional case report. METHODS: A 76-year-old man developed recurrent choroidal neovascularization at the new fovea after macular translocation surgery with 360-degree retinotomy. RESULTS: Two sessions of photodynamic therapy were applied, which resolved the choroidal neovascularization. Best-corrected visual acuity improved to 20/50 at the 6 and 12 months follow-up. CONCLUSION: Photodynamic therapy may be an option for treatment of recurrent choroidal neovascularization in the new subfoveal region after macular translocation surgery with 360-degree retinotomy.

Aged↗

Optical coherence tomographic findings of macular holes and retinal detachment after vitrectomy in highly myopic eyes.

PURPOSE: Macular holes cause retinal detachments in highly myopic eyes. Because degenerative macular changes often coexist, biomicroscopic evaluation of macular hole status after retinal reattachment is sometimes difficult. We studied macular holes with retinal detachment after vitrectomy using optical coherence tomography and evaluated the anatomic status of the hole and factors associated with anatomic success. DESIGN: Retrospective, nonrandomized, comparative study. PATIENTS: Sixteen eyes that underwent vitrectomy for retinal detachment associated with a macular hole were included. Internal limiting membrane peeling with indocyanine green was performed in 14 eyes; the epiretinal membrane was peeled with a diamond-dusted membrane scraper alone in two eyes. All retinas reattached postoperatively. The follow-up period at the optical coherence tomography examination was at least 6 months. METHODS: Optical coherence tomography was performed vertically and horizontally, and the presence of a persistent macular hole was determined. Other information was obtained from patient records. RESULTS: The macular holes closed in seven of 16 eyes (44%). Age, sex, axial length, preoperative best-corrected visual acuity, duration of symptoms, preoperative refractive error, and the preoperative area of the retinal detachment were not significantly correlated with hole closure. Improved postoperative best-corrected visual acuity (P <.05) was significantly associated with macular hole closure, and more frequent visual improvement (P =.06) was of borderline significance. CONCLUSIONS: The success rate was lower than those obtained in eyes without myopia or in myopic macular holes without retinal detachments. Macular hole closure may predict improved visual outcome for patients with retinal detachment and macular holes. Optical coherence tomography detects persistent macular holes in highly myopic eyes with retinal detachment.

Aged↗

Diagnosing dry eye using a blue-free barrier filter.

PURPOSE: To investigate the benefit of the blue-free barrier filter (BF filter) in diagnosing dry eye. DESIGN: Nonrandomized clinical comparison. METHODS: Fifty-three eyes with Sjögren syndrome (n = 42) or keratoconjunctivitis sicca (n = 11) were enrolled. Fluorescein staining was performed in temporal and nasal conjunctiva, and staining was scored with (BF score) and without the filter (FL score) from 0 to 3. Rose bengal staining was also scored (RB score) similarly. RESULTS: With FL scores of 0, 1, or 2, the BF score was significantly higher: 0.85 +/- 0.37 (P =.031), 1.74 +/- 0.65 (P =.001), and 2.65 +/- 0.48 (P =.001), respectively; with a FL score of 3, the BF score was 3 at all sites. The BF score was superior to the FL score in 66.6% of cases when the FL score was 0 and 1 and in 65.2% when the FL score was 2, but not when the FL score was 3. When the RB score was 0, 1, or 2, the BF score was higher: 1.88 +/- 0.92, 1.78 +/- 0.79, and 2.57 +/- 0.50, respectively (P =.001 for all); when the RB score was 3, the BF score was 2.97 +/- 0.16. The BF score was superior to the RB score in 75.5% of cases when the RB score was 0 and 1 and in 57.8% when the FL score was 2, but not in cases with a RB score of 3. CONCLUSIONS: The BF filter detects damaged conjunctival epithelium stained with fluorescein. Using the filter was beneficial in mild-to-moderate cases, not in severe cases. The BF filter allows diagnosis of dry eye even at the initial stage that is undetectable by conventional observation.

Adult↗

Early macular holes with retinoschisis in highly myopic eyes.

PURPOSE: We present two cases with early macular holes (MH) complicated by retinoschisis and foveal detachment (RSFD). DESIGN: Case reports. CASE REPORT: A 46-year-old woman and a 70-year-old woman, both with high myopia, presented visual loss and a small MH associated with RSFD. Vitrectomy and gas tamponade were performed. However, both MHs enlarged postoperatively, resulting in progressive retinal detachment. Additional gas tamponade led to retinal reattachment. At the final visit, the MH was open in case 1 but closed in case 2. CONCLUSIONS: Although the benefit of vitrectomy is uncertain, RSFD and MHs can be associated in highly myopic eyes.

Aged↗

Wavefront analysis in eyes with accommodative spasm.

PURPOSE: To investigate changes of spherical aberration in eyes with accommodative spasm. DESIGN: Case reports. METHODS: Four eyes of two patients with accommodative spasm were studied. Ocular spherical aberration was measured with a Hartmann-Shack wavefront aberrometer for the central 4-mm zone. RESULTS: The root mean square values of spherical aberration were negative (-0.086 +/- 0.026 microm root mean square). However, when the spasm of accommodation was cured or treated with a cycloplegic agent, the value shifted toward positivity (0.025 +/- 0.004 microm root mean square). CONCLUSIONS: Excessive accommodative tone is manifested objectively by negative spherical aberration in eyes with accommodative spasm.

Accommodation, Ocular↗

Electron microscopy of the epithelial flap created by ethanol treatment in the rabbit corneal epithelium.

PURPOSE: To assess the effect of corneal debridement with 25% ethanol on rabbit corneal epithelium by electron microscopy. SETTING: Department of Ophthalmology, Osaka University School of Medicine, Osaka, Japan. METHODS: Rabbit corneas were deepithelialized by applying 25% ethanol for 3 minutes, and a hinged epithelial flap was created and repositioned. Ten corneas were evaluated immediately after the epithelial debridement procedure and at 1, 3, and 7 days. Histological changes were evaluated using scanning and transmission electron microscopy. RESULTS: Corneas treated with ethanol showed a decrease in microvilli, breaks in intercellular junctions, epithelial cell edema, and damage in basement membrane hemidesmosomes. These toxic changes recovered to an almost normal appearance after 24 hours and rapidly improved over the following week. An increase in desquamated cells was observed after debridement; this returned to normal after 1 week according to the normal cellular cycle. Wing cells showed no damage at any stage. CONCLUSIONS: Although ethanol appeared to have a toxic effect on rabbit epithelial cells, the effect did not persist over time. The first signs of recovery were observed 24 hours after debridement, and full recovery was observed over the following week. The ethanol path to the central basement membrane appeared to be centripetally from a round cut through the basement membrane, leaving the wing cells intact.

Animals↗