Jong-Mo Seo

A suprachoroidal electrical retinal stimulator design for long-term animal experiments and in vivo assessment of its feasibility and biocompatibility in rabbits.

This article reports on a retinal stimulation system for long-term use in animal electrical stimulation experiments. The presented system consisted of an implantable stimulator which provided continuous electrical stimulation, and an external component which provided preset stimulation patterns and power to the implanted stimulator via a paired radio frequency (RF) coil. A rechargeable internal battery and a parameter memory component were introduced to the implanted retinal stimulator. As a result, the external component was not necessary during the stimulation mode. The inductive coil pair was used to pass the parameter data and to recharge the battery. A switch circuit was used to separate the stimulation mode from the battery recharging mode. The implantable stimulator was implemented with IC chips and the electronics, except for the stimulation electrodes, were hermetically packaged in a biocompatible metal case. A polyimide-based gold electrode array was used. Surgical implantation into rabbits was performed to verify the functionality and safety of this newly designed system. The electrodes were implanted in the suprachoroidal space. Evoked cortical potentials were recorded during electrical stimulation of the retina. Long-term follow-up using OCT showed no chorioretinal abnormality after implantation of the electrodes.

Development of microelectrode arrays for artificial retinal implants using liquid crystal polymers.

PURPOSE To develop a liquid crystal polymer (LCP)-based, long-term implantable, retinal stimulation microelectrode array using a novel fabrication method. METHODS The fabrication process used laser micromachining and customized thermal-press bonding to produce LCP-based microelectrode arrays. To evaluate the fabrication process and the resultant electrode arrays, in vitro reliability tests and in vivo animal experiments were performed. The in vitro tests consisted of electrode site impedance recording and electrode interlayer adhesion monitoring during accelerated soak tests. For in vivo testing, the fabricated electrode arrays were implanted in the suprachoroidal space of rabbit eyes. Optical coherence tomography (OCT) and electrically evoked cortical potentials (EECPs) were used to determine long-term biocompatibility and functionality of the implant. RESULTS The fabricated structure had a smooth, rounded edge profile and exhibited moderate flexibility, which are advantageous features for safe implantation without guide tools. After accelerated soak tests at 75 degrees C in phosphate-buffered saline, the electrode sites showed no degradation, and the interlayer adhesion of the structure showed acceptable stability for more than 2 months. The electrode arrays were safely implanted in the suprachoroidal space of rabbit eyes, and EECP waveforms were recorded. Over a 3-month postoperative period, no chorioretinal inflammation or structural deformities were observed by OCT and histologic examination. CONCLUSIONS LCP-based flexible microelectrode arrays can be successfully applied as retinal prostheses. The results demonstrate that such electrode arrays are safe, biocompatible, and mechanically stable and that they can be effective as part of a chronic retinal implant system.

The number of CD8+ T cells and NKT cells increases in the aqueous humor of patients with Behçet's uveitis

To determine whether there are differences in the immunopathogenesis of different endogenous uveitis syndromes, the phenotypic characteristics of immune cells were analysed among patients with endogenous uveitis. The aetiology of the uveitis included idiopathic recurrent acute anterior uveitis (18 patients), idiopathic intermediate uveitis (13 patients), Behçets uveitis (17 patients), Vogt–Koyanagi–Harada syndrome (7 patients), and so on. Flow cytometric analysis was performed using immune cells of the aqueous humor and the peripheral blood during the active phase of intraocular inflammation, and monoclonal antibodies to CD3, CD4, CD8, CD14, CD19, CD56, TCR γδ, pan TCR αβ and Vα24. CD8+ T cells were predominant in the aqueous humor of the patients with Behçets uveitis, whereas CD4+ T cells were mainly found in the aqueous humor of patients other than those with Behçets uveitis. The number of NKT (CD3+CD56+) cells was significantly higher both in the aqueous humor and the peripheral blood of the patients with Behçets uveitis compared with the other groups (P < 0·05). CD8+CD56+ cells were the predominant subtype of the increased NKT cells in patients with Behçets uveitis. In addition, intraocular infiltration of CD14+ cells significantly differed among the uveitis patients (P < 0·05). These results suggest that the immunopathogenesis of endogenous uveitis can vary between syndromes, and that CD8+CD56+ NKT cells may play an important role in the immunopathogenesis of Behçets uveitis.

Depression and the vision-related quality of life in patients with retinitis pigmentosa

Aims: To assess the relationship between depression and the vision-related quality of life in patients with retinitis pigmentosa (RP). Methods: The study included 144 patients diagnosed as having RP. The mean age of the patients was 38.5 (SD 13.3) years, and 42% of the subjects were women. They answered the National Eye Institute Visual Function Questionnaire (NEI-VFQ) to assess the vision-related quality of life and the Beck Depression Inventory (BDI) to assess depressive symptoms. Patients were classified into groups with and without depression according to the BDI score. The NEI-VFQ composite and subscale scores were compared between groups. The correlations between the BDI and the NEI-VFQ, weighted visual acuity (WVA) and functional vision score (FVS) were investigated. Results: The depressed group had significantly less subjective visual function compared with the non-depressed group. A negative correlation was observed between the BDI and the NEI-VFQ scores, while no correlation was found between the BDI score and WVA or FVS. Conclusion: The RP patients with depression had poorer vision-related functions compared with those patients without depression, which cannot be explained by the visual acuity. Interventions to diagnose and treat depression are necessary to enhance the overall quality of life in RP patients.

Alterations in hepatic metabolism of sulfur-containing amino acids induced by ethanol in rats

Summary. Alterations in hepatic metabolism of S-amino acids were monitored over one week in male rats treated with a single dose of ethanol (3 g/kg, ip). Methionine and S-adenosylhomocysteine concentrations were increased rapidly, but S-adenosylmethionine, cysteine, and glutathione (GSH) decreased following ethanol administration. Activities of methionine adenosyltransferase, cystathionine γ-lyase and cystathionine β-synthase were all inhibited. γ-Glutamylcysteine synthetase activity was increased from t = 8 hr, but GSH level did not return to control for 24 hr. Hepatic hypotaurine and taurine levels were elevated immediately, but reduced below control in 18 hr. Changes in serum and urinary taurine levels were consistent with results observed in liver. Cysteine dioxygenase activity was increased rapidly, but declined from t = 24 hr. The results show that a single dose of ethanol induces profound changes in hepatic S-amino acid metabolism, some of which persist for several days. Ethanol not only inhibits the cysteine synthesis but suppresses the cysteine availability further by enhancing its irreversible catabolism to taurine, which would play a significant role in the depletion of hepatic GSH.

Accommodative Response of Integral Imaging in Near Distance

Objective evaluation results using optometric device to measure accommodative responses in viewing a real object and integral imaging are presented. From the empirical results between the real object and an integrated three-dimensional (3D) image, we find that over 73% of participants keep eyes on the real integrated 3D image instead of a display panel. The results also show the participants do not recognize a mismatch between the accommodative response and the convergence of the eye, which used to be believed as one of the major factors to cause visual fatigue in viewing near-distance integral imaging. Seventy-one normal adult subjects (23 ~ 38 years old) participated in the experiment, and accommodative response measurement results of the real integrated image show a statistically significant concordance with real objects.

In Vitro Biocompatibility of Various Polymer-Based Microelectrode Arrays for Retinal Prosthesis

PURPOSE The purpose of our study is to evaluate the biocompatibility of various polymers used as microelectrode arrays (MEAs) in retinal prostheses through in vitro cytotoxicity testing following a standardized METHOD METHODS Three types of polymer-based MEAs were examined: silicone-based platinum, polyimide-based gold and liquid crystal polymer (LCP)-based gold MEAs. The silicone/platinum MEAs were fabricated by a Nd:YAG laser, polyimide/gold MEAs by a semiconductor manufacturing technique, and LCP/gold MEAs by laser micromachining and thermal-bonding process. All experimental procedures followed the International Organization for Standardization (ISO) 10993-5. To obtain the extracts of specimens, 4 g of each type of MEA were eluted by culture media, MEM, for 24 hours. Then, several diluents of extracts, including the original extracts, were applied to a cultured-cell monolayer, L929 fibroblasts. The morphologic changes of cells were analyzed by microscope after 24 and 48 hours of incubation. The quantitative evaluations of cell viability were performed by MTT assay after 24 hours of incubation. RESULTS The microscopic evaluations revealed that extracts from polymer-based MEAs did not induce morphologic changes or reduction of cells compared with control irrespective of concentrations of extracts. The MTT assay showed high viability values of approximately 80 to 130% regardless of diluted ratio of extracts from polymer-based MEAs. None of the polymers demonstrated a significant reduction of cell viability when compared with control. CONCLUSIONS All types of polymer-based MEAs, including silicone/platinum, polyimide/gold, and LCP/gold MEAs, meet the criteria of biocompatibility guided by international standards, ISO 10993-5.

Feasibility of microelectrode array (MEA) based on silicone-polyimide hybrid for retina prosthesis.

PURPOSE To adopt micropatterning technology in manufacturing silicone elastomer-based microelectrode arrays for retinal stimulation, a silicone-polyimide hybrid microelectrode array was proposed and tested in vivo. METHODS Gold microelectrodes were created by semiconductor manufacturing technology based on polyimide and were hybridized with silicone elastomer by spin coating. The stability of the hybrid between the two materials was flex and blister tested. The feasibility of the hybrid electrode was evaluated in the rabbit eye by reviewing optical coherence tomography (OCT) findings after suprachoroidal implantation. RESULTS The flex test showed no dehiscence between the two materials for 24 hours of alternative flexion and extension from -45.0 degrees to +45.0 degrees . During the blister test, delamination was observed at 8.33 +/- 1.36 psi of pressure stress; however, this property was improved to 11.50 +/- 1.04 psi by oxygen plasma treatment before hybridization. OCT examination revealed that the implanted electrodes were safely located in the suprachoroidal space during the 4-week follow-up period. CONCLUSIONS The silicone-polyimide hybrid microelectrode array showed moderate physical properties, which are suitable for in vivo application. Appropriate pretreatment before hybridization improved electrode stability. In vivo testing indicated that this electrode is suitable as a stimulation electrode in artificial retina.

A Miniaturized, Eye-Conformable, and Long-Term Reliable Retinal Prosthesis Using Monolithic Fabrication of Liquid Crystal Polymer (LCP)

A novel retinal prosthetic device was developed using biocompatible liquid crystal polymer (LCP) to address the problems associated with conventional metal- and polymer-based devices: the hermetic metal package is bulky, heavy, and labor-intensive, whereas a thin, flexible, and MEMS-compatible polymer-based system is not durable enough for chronic implantation. Exploiting the advantageous properties of LCP such as a low moisture absorption rate, thermobonding, and thermoforming, we fabricate a small, light-weight, long-term reliable retinal prosthesis that can be conformally attached on the eye-surface. A LCP fabrication process using monolithic integration and conformal deformation was established enabling miniaturization and a batch manufacturing process as well as eliminating the need for feed-through technology. The functionality of the fabricated device was tested through wireless operation in saline solution. Its efficacy and implantation stability were verified through in vivo animal tests by measuring the cortical potential and monitoring implanted dummy devices for more than a year, respectively.

Fabrication of Pillar Shaped Electrode Arrays for Artificial Retinal Implants

Polyimide has been widely applied to neural prosthetic devices, such as the retinal implants, due to its well-known biocompatibility and ability to be micropatterned. However, planar films of polyimide that are typically employed show a limited ability in reducing the distance between electrodes and targeting cell layers, which limits site resolution for effective multi-channel stimulation. In this paper, we report a newly designed device with a pillar structure that more effectively interfaces with the target. Electrode arrays were successfully fabricated and safely implanted inside the rabbit eye in suprachoroidal space. Optical Coherence Tomography (OCT) showed well-preserved pillar structures of the electrode without damage. Bipolar stimulation was applied through paired sites (6:1) and the neural responses were successfully recorded from several regions in the visual cortex. Electrically evoked cortical potential by the pillar electrode array stimulation were compared to visual evoked potential under full-field light stimulation.