Masashi Mimura

Changes in expression of aquaporin-4 and aquaporin-9 in optic nerve after crushing in rats.

The purpose of this study was to determine the temporal and spatial changes in the expression of AQP4 and AQP9 in the optic nerve after it is crushed. The left optic nerves of rats were either crushed (crushed group) or sham operated (sham group), and they were excised before, and at 1, 2, 4, 7, and 14 days later. Four optic nerves were pooled for each time point in both groups. The expression of AQP4 and AQP9 was determined by western blot analyses. Immunohistochemistry was used to determine the spatial expression of AQP4, AQP9, and GFAP in the optic nerve. Optic nerve edema was determined by measuring the water content in the optic nerve. The barrier function of the optic nerve vessels was determined by the extravasated Evans blue dye on days 7 and 14. The results showed that the expression of AQP4 was increased on day 1 but the level was significantly lower than that in the sham group on days 4 and 7 (P<0.05). In contrast, the expression of AQP9 gradually increased, and the level was significantly higher than that in the sham group on days 7 and 14 (P<0.05, Tukey-Kramer). The down-regulation of AQP4 was associated with crush-induced optic nerve edema, and the water content of the nerve was significantly increased by 4.3% in the crushed optic nerve from that of the untouched fellow nerve on day 7. The expression of AQP4 and GFAP was reduced at the crushed site where AQP4-negative and AQP9-positive astrocytes were present. The barrier function was impaired at the crushed site on days 7 and 14, restrictedly where AQP4-negative and AQP9-positive astrocytes were present. The presence of AQP9-positive astrocytes at the crushed site may counteract the metabolic damage but this change did not fully compensate for the barrier function defect.

Nitric Oxide Increases the Expression of Aquaporin-4 Protein in Rat Optic Nerve Astrocytes through the Cyclic Guanosine Monophosphate/Protein Kinase G Pathway

Aims: Nitric oxide (NO) is associated with neuroinflammation in the central nervous system. We determined whether NO increases the expression of aquaporin-4 (AQP4) in optic nerve astrocytes of rats. Methods: Isolated astrocytes were incubated under normoxic or hypoxic conditions with or without glucose (5.5 mM). The astrocytes were also exposed to different concentrations of S-nitroso-N-acetyl-DL-penicillamine (SNAP, 1.0-100 μM), an NO donor. The expression of AQP4 was determined by Western blot analyses, and NO formation was measured by the Griess reaction. The changes in astrocytic cellular volumes were determined by flow cytometry. Results: Hypoxia and glucose deprivation increased AQP4 expression and NO formation. Inhibition of NO synthetase (NOS) significantly suppressed these changes. SNAP caused a significant increase in AQP4 expression, and the increase was significantly suppressed by carboxy-PTIO, a scavenger of NO. Incubation with 8-Br-cyclic guanosine monophosphate (cGMP) mimicked the effects of SNAP, while the addition of either 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ; inhibitor of soluble guanylate cyclase) or KT5823 (protein kinase G inhibitor) suppressed the SNAP-induced increase in AQP4 significantly. SNAP also caused a significant increase in astrocytic cellular volume through the AQP4 channels. Conclusions: NO increased the AQP4 expression of optic nerve astrocytes through the cGMP/protein kinase G pathway and enlarged their volume.

Optical Coherence Tomography in an Infant with Walker-Warburg Syndrome.

Purpose: Walker-Warburg syndrome (WWS) is a type of congenital muscular dystrophy (CMD) characterised by severe brain malformation, lissencephaly, and congenital eye abnormalities. Despite the coexistence of various eye abnormalities, results from optical coherence tomography (OCT) in WWS have not previously been reported. We herein report specific OCT findings in an infant with WWS. Patients and Methods: The patient was a 14-day-old boy delivered by caesarean section at 38 weeks and 4 days of gestation and with a birth weight of 2,543 g. A cranial MRI showed lissencephaly, hydrocephalus, an encephalocele, and cerebellar hypoplasia, consistent with the diagnosis of WWS. Results: A bilateral ocular examination showed no abnormalities of the anterior eye segment. A fundus examination showed a persistent hyaloid artery in the vitreous cavity, a widespread loss of fundus pigmentation, transparent choroidal vessels (some choroidal vessel sections were visible), and the absence of a distinct macular reflex. OCT showed no foveal pit and an indistinct laminar structure of the retina. The infant subsequently developed congenital glaucoma and he then died of respiratory failure at the age of 8 months. Conclusions: WWS is associated with a high incidence of congenital eye abnormalities, and this infant showed findings consistent with WWS. OCT revealed a marked retinal dysplasia.

P7C3 Suppresses Neuroinflammation and Protects Retinal Ganglion Cells of Rats from Optic Nerve Crush

Purpose To determine whether P7C3-A20 can inhibit the phosphorylation of the mammalian target of rapamycin (mTOR), depress neuroinflammation, and protect retinal ganglion cells (RGCs) of rats from optic nerve crush (ONC). Methods The left optic nerve was crushed, and 5.0 mg/kg/d of P7C3-A20, 1.0 mg/kg/d of rapamycin, or their vehicle was injected intraperitoneally for 3 consecutive days beginning 1 day before the ONC. The protective effects on the RGCs were determined by immunohistochemical staining for Tuj-1. The level of phosphorylated mTOR was determined by immunoblotting. The neuroinflammation in the optic nerve was determined by changes in the expression of CD68, TNF-α, MCP-1, and iNOS. Results The density of Tuj-1-stained cells in the control was 2010 ± 81.5/mm2 and 1842 ± 80.4/mm2 on days 7 and 14 after the sham operation. These levels were lower at 995 ± 122/mm2 and 450 ± 52.4/mm2 on days 7 and 14 after the ONC, respectively. Rapamycin and P7C3-A20 preserved the density at significantly higher levels on both days (P < 0.05, Scheffe test). The level of phosphorylated mTOR increased by 1.56-fold above the control level on day 7. Rapamycin and P7C3 significantly lowered the level of phosphorylated mTOR to 0.89-fold and 0.67-fold of the control, respectively. There was an accumulation of CD68+ cells that were immunoreactive to TNF-α at the crush site. The expression of MCP-1 and iNOS was increased chiefly in the astrocytes around the lesion. These inflammatory events were suppressed by both rapamycin and P7C3. Conclusions P7C3-A20 can inhibit mTOR phosphorylation in the crushed optic nerve, which may suppress neuroinflammation and preserve the RGCs.

Process of spontaneous resolution in the conservative management of congenital dacryocystocele

Purpose To assess efficacy of the conservative management of patients with congenital dacryocystocele. Materials and methods This was a retrospective case series involving six sides of five infants with a dacryocystocele treated at Osaka Kaisei Hospital, Osaka, Japan. The conservative management protocol consisted of the application of warm compresses and massage over the mass, with the addition of antibiotics when dacryocystitis developed. Patient age at the time of resolution, presence of retrograde outflow of contents of dacryocystoceles from the puncta, and development of dacryocystitis were recorded. Results The dacryocystocele was unilateral in four patients and bilateral in one patient. A nasal cyst was present in four patients without respiratory distress. The median patient age at the time of the diagnosis was 7 days (range 2–10 days). Conservative management was selected in all patients, and the dacryocystocele was resolved in all patients at a median patient age of 14.5 days (range 11–105 days). Two sides developed dacryocystitis, which resolved in a few days with antibiotic treatment. In those two sides, rupture of the dacryocystoceles to the common canaliculus with retrograde discharge of the contents from the puncta before the dacryocystitis developed was noted. For the other four treated sides, no such discharge or development of dacryocystitis was observed. Conclusion The findings of this study show that a dacryocystocele has a good chance of resolving spontaneously with conservative management and careful observation, and that rupture of the dacryocystocele to the common canaliculus might be an important precursor of dacryocystitis.

Investigation of scleral thermal injuries caused by ultrasonic pars plana phacoemulsification and aspiration using pig eyes

PurposeThe purpose of this study was to investigate the thermal injuries caused by ultrasonic pars plana phacoemulsification and aspiration (PPPEA) using pig eyes.MethodUsing a 20-gauge (G) vitrectomy system (Accurus®, Fragmatome; Alcon Laboratories) in both the ‘open-tip’ and ‘closed-tip’ techniques, PPPEA was performed in pig eyes and the subsequent thermal injuries generated around the scleral wound were measured by infrared thermal imaging (thermography). Post surgery, the state of the scleral wound was observed under a microscope, and a tissue slice containing the scleral wound was then prepared and observed under an optical microscope.ResultsThermography measurements revealed a slight temperature rise around the scleral wound in the open-tip case, yet a marked temperature rise in the closed-tip case. The scleral wound incision produced by the open tip was linear, while that produced by the closed tip was expanded. Histological examination revealed mild degeneration of the sclera around the wound in the open-tip case, yet marked tissue degeneration by thermal injuries in the closed-tip case.ConclusionOur findings showed that in PPPEA, the temperature of the tip of a 20G vitrectomy system rapidly increases due to the closed-tip technique, thus producing obvious thermal damage to the scleral wound. In order to prevent thermal injuries to the scleral wound during PPPEA, it is important to shorten the time of ultrasonic oscillation during surgery as much as possible while the tip is occluded with nuclear fragments.

Case Report of a Family Affected by Stickler Syndrome in Which Rhegmatogenous Retinal Detachment Occurred in Five Eyes of Three Siblings

Purpose: Stickler syndrome is an autosomal dominant inherited disorder that is well known to be highly associated with the development of rhegmatogenous retinal detachment. In this study, we report the case of a family affected by Stickler syndrome in which rhegmatogenous retinal detachment developed in 5 eyes of 3 siblings. Case Series: For treatment, we performed vitreous surgery on 1 eye of the eldest son, and bilateral scleral buckling surgery on the 2 younger children. A good postoperative outcome was obtained on the 4 eyes that underwent scleral buckling surgery, yet the prognosis was poor on the 1 eye that underwent vitrectomy due to redetachment of the retina and corneal complication. Since vitreous surgery was quite difficult due to strong vitreoretinal adhesion, we created an artificial posterior vitreous detachment via the bimanual technique combined with encircling. For the scleral buckling surgery, broad scleral extrusion was needed to seal multiple retinal breaks. Conclusions: The findings of this study showed a high prevalence of rhegmatogenous retinal detachment in a single family with Stickler syndrome. In these cases, scleral buckling surgery was effective for treating the detached retina, and some prophylactic treatment, such as laser photocoagulation to prevent the occurrence of rhegmatogenous retinal detachment, should be considered for such cases in the future.

A case of neglected silicone tube in lacrimal duct for 20 years

Purpose To report a case of prolonged placement of a lacrimal silicone tube for 20 years, with evaluation of the lacrimal duct using lacrimal micro-endoscopy and inspection of deformation of the lacrimal tube. Observations This study involved a case of dacryocystitis in which a silicone tube had been placed in the patient 20-years previous and that was treated conservatively. Although granulation tissue formation due to dacryocystitis in the lacrimal duct was observed under lacrimal micro-endoscopy, subjective and objective resolution of symptoms, including granulated tissue formation, was achieved after removal of the silicone tube and conservative medical treatment. Follow-up examinations performed over a 12-month period post treatment revealed no recurrence of epiphora or anatomical obstruction. Inspection of the lacrimal tube using the tension test revealed minimal changes in the tube in situ for 20 years. Conclusions and Importance The findings in this case suggest both the lacrimal system and the silicone tube are tolerant to prolonged intubation, as long as the tube had been placed properly with careful observation. Our findings may encourage physicians to consider prolonged intubation for select cases of nasolacrimal duct obstruction.

Case of asteroid hyalosis that developed severely reduced vision after cataract surgery

BackgroundTo report our findings in a patient with asteroid hyalosis (AH) who had a severe reduction of his visual acuity following cataract surgery. The vision was improved by vitreous surgery.Case presentationThe patient was an 81-year-old man. Following cataract surgery on his left eye, his decimal best-corrected visual acuity (BCVA) was markedly reduced from 0.2 to 0.02. A large number of asteroid bodies (ABs) was observed to be concentrated on the posterior surface of the implanted intraocular lens. Ultrasound B-mode images showed turbidity of the vitreous that was denser in the anterior vitreous where the ABs were concentrated. During vitrectomy, the ABs were observed to be concentrated in the anterior vitreous cavity, and a complete posterior vitreous detachment (PVD) was present. After vitrectomy successfully removed the ABs, the visibility of the fundus improved and the BCVA recovered to 1.0.ConclusionWe suggest that the visual impairment after the cataract surgery was due to the concentrated ABs in the anterior vitreous cavity. The clustering of the ABs in the anterior vitreous cavity was most likely caused by the PVD that developed during the cataract surgery.

Contents Vol. 54, 2015

Basel • Freiburg • Paris • London • New York • Chennai • New Delhi • Bangkok • Beijing • Shanghai • Tokyo • Kuala Lumpur • Singapore • Sydney Journal for Translational and Clinical Research Founded 1970 by O. Hockwin, Bonn, G. Naumann, Hamburg and D.F. Cole, London Continued by O. Hockwin, Bonn (1981–1994); G.F.J.M. Vrensen, Zeist (1994–2003); Uwe Pleyer, Berlin (2003–2014); David E. Pelayes, Buenos Aires, Borja Corcόstegui, Barcelona (2012–2014)