Takayuki Okano

Room temperature continuous wave operation of a surface-emitting two-dimensional photonic crystal diode laser

We achieved room temperature continuous wave operation of a surface-emitting two-dimensional photonic crystal diode laser by current injection. This is the first time ever that room temperature continuous wave operation of a photonic crystal diode laser has been realized. This laser features single mode oscillation over a large area, which is impossible for conventional lasers. In this work, we optimized the epitaxial layer composition for better carrier confinement and clarified the relationship between the diameter of the air holes in the photonic crystal and the threshold current of the laser in order to estimate the optimized threshold current.

Novel therapy for hearing loss: delivery of insulin-like growth factor 1 to the cochlea using gelatin hydrogel.

Hypothesis: Local application of recombinant human insulin-like growth factor 1 (rhIGF-1) via a biodegradable hydrogel after onset of noise-induced hearing loss (NIHL) can attenuate functional and histologic damage. Background: The biodegradable gelatin hydrogel makes a complex with drugs by static electric charges and releases drugs by degradation of gelatin polymers. We previously demonstrated the efficacy of local rhIGF-1 application via hydrogels before noise exposure for prevention of NIHL. Methods: First, we used an enzyme-linked immunosorbent assay to measure human IGF-1 concentrations in the cochlear fluid after placing a hydrogel containing rhIGF-1 onto the round window membrane of guinea pigs. Second, the functionality and the histology of guinea pig cochleae treated with local rhIGF-1 application at different concentrations after noise exposure were examined. Control animals were treated with a hydrogel immersed in physiologic saline alone. Results: The results revealed sustained delivery of rhIGF-1 into the cochlear fluid via the hydrogel. The measurement of auditory brainstem responses demonstrated that local rhIGF-1 treatment significantly reduced the threshold elevation from noise. Histologic analysis exhibited increased survival of outer hair cells by local rhIGF-1 application through the hydrogel. Conclusion: These findings indicate that local rhIGF-1 treatment via gelatin hydrogels is effective for treatment of NIHL.

Lasing band-edge identification for a surface-emitting photonic crystal laser

The possibility of single-mode oscillation over a large cavity area for photonic crystal lasers emitting at the photonic band edge has resulted in much interest in such materials for new forms of solid-state laser. In this paper, we measure the photonic bandstructure in our sample and identify the lasing band edge. By mapping out the bandstructure at the /spl Gamma/-point, we have observed fine structure at the band edge. The experimental results are in good agreement with the theoretically predicted bandstructure. Above threshold, we observe a lasing peak at 965 nm at one of the band edges. The far-field distribution of the laser is measured, showing an annular profile and azimuthal polarization. Calculations on the far-field distribution at the lasing band edge suggest the annular profile is due to an anti-symmetric resonant mode.

Myosin II regulates extension, growth and patterning in the mammalian cochlear duct

The sensory epithelium of the mammalian cochlea comprises mechanosensory hair cells that are arranged into four ordered rows extending along the length of the cochlear spiral. The factors that regulate the alignment of these rows are unknown. Results presented here demonstrate that cellular patterning within the cochlea, including the formation of ordered rows of hair cells, arises through morphological remodeling that is consistent with the mediolateral component of convergent extension. Non-muscle myosin II is shown to be expressed in a pattern that is consistent with an active role in cellular remodeling within the cochlea, and genetic or pharmacological inhibition of myosin II results in defects in cellular patterning that are consistent with a disruption in convergence and extension. These results identify the first molecule, myosin II, which directly regulates cellular patterning and alignment within the cochlear sensory epithelium. Our results also provide insights into the cellular mechanisms that are required for the formation of highly ordered cellular patterns.

Bone marrow-derived cells expressing Iba1 are constitutively present as resident tissue macrophages in the mouse cochlea

Immune‐mediated inner ear disorder has been well established as a clinical entity; however, the innate immune system of the inner ear is a poorly understood area of research with high clinical and immunological importance. Although the presence of resident tissue macrophages in the inner ear has been suggested, there has been some controversy. In this study, we analyzed the origin of cochlear resident macrophages and the contribution of hematopoietic bone marrow (BM) to the recruitment of macrophages in the cochlea. To visualize the localization of BM‐derived cells, BM chimeric mice were made by transplantation of hematopoietic stem cells, which were genetically labeled with enhanced green fluorescent protein, into lethally irradiated C57BL/6 mice. The distribution and characteristics of BM‐derived cells in the mouse cochlea were studied immunohistochemically. We successfully identified the constitutive presence of tissue resident macrophages in the spiral ligament and spiral ganglion that are derived from BM in larger numbers than previously reported. Moreover, cochlear resident macrophages gradually turn over for several months during steady‐state replacement by BM‐derived cells, and the number of cochlear macrophages immediately increased in response to local surgical stress. The present findings demonstrate the hematopoietic origin of cochlear resident and infiltrating macrophages. Our study provides a novel anatomical and immunological basis for the inner ear and indicates that the cochlear resident macrophages would be a therapeutic target in inner ear disorders.

Insulin-Like Growth Factor Signaling Regulates the Timing of Sensory Cell Differentiation in the Mouse Cochlea

The mammalian auditory sensory epithelium, the organ of Corti, is a highly ordered cellular structure that comprises two types of auditory hair cells and several types of nonsensory supporting cells. During embryogenesis, a stereotyped sequence of cellular and molecular events is required for its development. These processes are assumed to be regulated by multiple growth and transcription factors. However, the majority of these factors have not been identified. One potential regulator of cochlear development is the insulin-like growth factor (IGF) signaling family. To examine the roles of the IGF pathway in inner ear formation, cochleae from Igf1r mutant mice were analyzed. Deletion of Igf1r leads to several changes in inner ear development including a shortened cochlear duct, a decrease in the total number of cochlear hair cells, and defects in the formation of the semicircular canals. In addition, maturation of the cochlear sensory epithelium was delayed at the transition point between cellular proliferation and differentiation. To determine the molecular basis for these defects, inhibition of IGF signaling was replicated pharmacologically in vitro. Results indicated that IGF signaling regulates cochlear length and hair cell number as well as Atoh1 expression through the phosphatidylinositol 3-kinase/Akt signaling pathway. These results demonstrate novel roles for IGF signaling in inner ear development including regulation of vestibular formation, length of the cochlear duct, and the number of cochlear hair cells. The results also provide new insights regarding the pathological processes that underlie auditory defects in the absence of IGF signaling in both humans and mice.

Immune system of the inner ear as a novel therapeutic target for sensorineural hearing loss

Sensorineural hearing loss (SNHL) is a common clinical condition resulting from dysfunction in one or more parts in the auditory pathway between the inner ear and auditory cortex. Despite the prevalence of SNHL, little is known about its etiopathology, although several mechanisms have been postulated including ischemia, viral infection or reactivation, and microtrauma. Immune-mediated inner ear disease has been introduced and accepted as one SNHL pathophysiology; it responds to immunosuppressive therapy and is one of the few reversible forms of bilateral SNHL. The concept of immune-mediated inner ear disease is straightforward and comprehensible, but criteria for clinical diagnosis and the precise mechanism of hearing loss have not been determined. Moreover, the therapeutic mechanisms of corticosteroids are unclear, leading to several misconceptions by both clinicians and investigators concerning corticosteroid therapy. This review addresses our current understanding of the immune system in the inner ear and its involvement in the pathophysiology in SNHL. Treatment of SNHL, including immune-mediated inner ear disorder, will be discussed with a focus on the immune mechanism and immunocompetent cells as therapeutic targets. Finally, possible interventions modulating the immune system in the inner ear to repair the tissue organization and improve hearing in patients with SNHL will be discussed. Tissue macrophages in the inner ear appear to be a potential target for modulating the immune response in the inner ear in the pathophysiology of SNHL.

Surgical Invasiveness of Cell Transplantation into the Guinea Pig Cochlear Modiolus

Objective: Previous studies have demonstrated the potential of cell transplantation for regeneration of spiral ganglion neurons (SGNs). However, the effect of surgical invasion on host cochleae has yet to be evaluated. The present study investigated the efficiency and invasiveness of our surgical procedure using a fine glass pipette for injections into the cochlear modiolus. Methods: We examined the survival of transplanted embryonic stem cell-derived neurons in the cochlear modiolus of guinea pigs. Surgical invasiveness was assessed by measurements of electrically evoked auditory brainstem responses (eABRs) and SGN densities after an injection of 5 ml of saline into the cochlear modiolus. Results: All of the transplanted animals exhibited localization of transplanted cells in the cochlear modiolus. No significant alterations in the eABR thresholds or SGN densities were found following surgery. Conclusion: These findings indicate that our procedure is a viable method for testing the potential of transplants for SGN replacement.

Linearly-Polarized Single-Lobed Beam in a Surface-Emitting Photonic-Crystal Laser

A linearly-polarized, single-lobed beam has been demonstrated in a surface-emitting photonic-crystal laser under single-mode operation by employing fine-tuned elliptical lattice points and π-phase shift. A crystal structure, including the elliptical lattice points with a short/long axis ratio of 0.95, has been successfully fabricated. The resulting beam was strongly polarized in one direction, although the shape of the lattice points was nearly circular. It was found that two-dimensional optical coupling was compatible with strong linear polarization.

Distribution of bone marrow-derived cells in the vestibular end organs and the endolymphatic sac

Abstract Conclusion: Bone marrow-derived cells (BMDCs) are constitutively present in the vestibular end organs and in the endolymphatic sac, and may play a role in the maintenance of inner ear homeostasis. Objectives: The aim was to examine the distribution and characteristics of BMDCs in the vestibular end organs and in the endolymphatic sac. Methods: Bone marrow-chimeric mice were generated by bone marrow transplantation from mice genetically labeled with enhanced green fluorescent protein to C57 Bl/6 mice to visualize BMDCs. Three months after bone marrow transplantation, inner ear specimens were processed for histochemical analyses. Results: BMDCs were widely distributed in the vestibular end organs and the endolymphatic sac, whereas there were differences in the phenotype and the distribution between the vestibular end organs and the endolymphatic sac. A subpopulation of BMDCs in the vestibular end organs expressed antigen-presenting protein MHC class II. Moreover, the density of BMDCs in the vestibular end organs increased in response to local mechanical stress.