Yu Jeong Kim

Engineered superparamagnetic Mn0.5Zn0.5Fe2O4 nanoparticles as a heat shock protein induction agent for ocular neuroprotection in glaucoma

Ocular neuroprotection induced by localized heat shock proteins (HSPs) has been paid considerable attention as an efficacious treatment modality for glaucoma. However, the current clinical approaches to induce HSPs in the retinal ganglion cells (RGCs) are limited due to undesirable side effects. Here, we present that the induction of HSPs by local magnetic hyperthermia using engineered superparamagnetic Mn(0.5)Zn(0.5)Fe(2)O(4) nanoparticle agents (EMZF-SPNPAs) with a 5.5 nm mean particle size is promisingly feasible for a physiologically tolerable ocular neuroprotection modality. The sufficiently high specific absorption rate (SAR) (∼256.4 W/g in an agar solution) achieved at the biologically safe range of applied AC magnetic field and frequency as well as the superior biocompatibility of EMZF-SPNPA, which were confirmed from both in-vitro and in-vivo animal pilot studies, allowing it to be considered as a potential localized HSPs agent. Furthermore, the successful demonstration of a newly designed infusion technique, which diffuses the EMZF-SPNPAs through the vitreous body to the retina in a rat eye, more strongly verified the promises of this biotechnical approach to the ocular neuroprotection modality in glaucoma clinics.

Effects of Mn concentration on the ac magnetically induced heating characteristics of superparamagnetic MnxZn1−xFe2O4 nanoparticles for hyperthermia

The effects of Mn2+ cation concentration on the ac magnetically induced heating characteristics and the magnetic properties of superparamagnetic MnxZn1−xFe2O4 nanoparticles (SPNPs) were investigated to explore the biotechnical feasibility as a hyperthermia agent. Among the MnxZn1−xFe2O4 SPNPs, the Mn0.5Zn0.5Fe2O4 SPNP showed the highest ac magnetically induced heating temperature (ΔTac,mag), the highest specific absorption rate (SAR), and the highest biocompatibility. The higher out of phase susceptibility (χm″) value and the higher chemical stability systematically controlled by the replacement of Zn2+ cations by the Mn2+ cations on the A-site (tetrahedral site) are the primary physical reason for the promising biotechnical properties of Mn0.5Zn0.5Fe2O4 SPNP.

Effects of Recovery Time during Magnetic Nanofluid Hyperthermia on the Induction Behavior and Efficiency of Heat Shock Proteins 72

In this study, we investigated the effects of recovery time during magnetic nanofluid hyperthermia (MNFH) on the cell death rate and the heat shock proteins 72 (HSP72) induction behavior in retinal ganglion cells (RGCs-5) to provide a possible solution for highly efficient ocular neuroprotection. The recovery time and the heat duration time during MNFH were systematically controlled by changing the duty cycle of alternating current (AC) magnetic field during MNFH. It was clearly observed that the cell death rate and the HSP72 induction rate had a strong dependence on the recovery time and the optimizated recovery time resulted in maximizing the induction efficiency of HSP72. Controlling the recovery time during MNFH affects not only the cell death rate but also HSP72 induction rate. The cell death rate after MNFH was dramatically decreased by increasing the recovery time during MNFH. However, it was also found that the HSP72 induction rate was slightly decreased by increasing the recovery time. These results indicate that applying the appropriate or optimized recovery time during MNFH can improve the induction efficiency of HSP72 by minimizing the cell death caused by cytotoxic effects of heat.

Imaging of single retinal ganglion cell with differential interference contrast microscopy (Conference Presentation)

Glaucoma is a progressive optic neuropathy, characterized by the selective loss of retinal ganglion cells (RGCs). Therefore, monitoring the change of number or morphology of RGC is essential for the early detection as well as investigation of pathophysiology of glaucoma. Since RGC layer is transparent and hyporeflective, the direct optical visualization of RGCs has not been successful so far. Therefore, glaucoma evaluation mostly depends on indirect diagnostic methods such as the evaluation of optic disc morphology or retinal nerve fiber layer thickness measurement by optical coherence tomography. We have previously demonstrated single photoreceptor cell imaging with differential interference contrast (DIC) microscopy. Herein, we successfully visualized single RGC using DIC microscopy. Since RGC layer is much less reflective than photoreceptor layer, various techniques including the control of light wavelength and bandwidth using a tunable band pass filter were adopted to reduce the chromatic aberration in z-axis for higher and clearer resolution. To verify that the imaged cells were the RGCs, the flat-mounted retina of Sprague-Dawley rat, in which the RGCs were retrogradely labeled with fluorescence, was observed by both fluorescence and DIC microscopies for direct comparison. We have confirmed that the cell images obtained by fluorescence microscopy were perfectly matched with cell images by DIC microscopy. As conclusion, we have visualized single RGC with DIC microscopy, and confirmed with fluorescence microscopy.

Detection of retinitis pigmentosa by differential interference contrast microscopy.

Differential interference contrast microscopy is designed to image unstained and transparent specimens by enhancing the contrast resulting from the Nomarski prism-effected optical path difference. Retinitis pigmentosa, one of the most common inherited retinal diseases, is characterized by progressive loss of photoreceptors. In this study, Differential interference contrast microscopy was evaluated as a new and simple application for observation of the retinal photoreceptor layer and retinitis pigmentosa diagnostics and monitoring. Retinal tissues of Royal College of Surgeons rats and retinal-degeneration mice, both well-established animal models for the disease, were prepared as flatmounts and histological sections representing different elapsed times since the occurrence of the disease. Under the microscopy, the retinal flatmounts showed that the mosaic pattern of the photoreceptor layer was irregular and partly collapsed at the early stage of retinitis pigmentosa, and, by the advanced stage, amorphous. The histological sections, similarly, showed thinning of the photoreceptor layer at the early stage and loss of the outer nuclear layer by the advanced stage. To count and compare the number of photoreceptors in the normal and early-retinitis pigmentosa-stage tissues, an automated cell-counting program designed with MATLAB, a numerical computing language, using a morphological reconstruction method, was applied to the differential interference contrast microscopic images. The number of cells significantly decreased, on average, from 282 to 143 cells for the Royal College of Surgeons rats and from 255 to 170 for the retinal-degeneration mouse. We successfully demonstrated the potential of the differential interference contrast microscopy technique’s application to the diagnosis and monitoring of RP.