-
[show abstract]
[hide abstract]
ABSTRACT: To study RhoA activation and the effect of the Rho-kinase inhibitor in the development of retinal neovascularization in a mouse model of oxygen-induced retinopathy (OIR).
C57BL/6 mice at postnatal day (P7) were exposed to hyper-oxygen for 5 days and returned to room air for 5 days to induce OIR. RhoA-GTP, an active form of RhoA, in retinas at P12, P13 and P17 was detected. Mice received a single intravitreal injection of Y27632 (5 µM or 50 µM), a Rho-kinase inhibitor, in one eye during the transition from oxygen to room air at P12. Contralateral eyes were used as the control. Fluorescein-conjugated dextran angiography of retinal whole mount was prepared to score features of neovascular retinopathy at P17. The preretinal neovascular nuclei quantification was performed in frozen sections as well to evaluate the neovascularization.
The retinal RhoA-GTP in OIR mice significantly increased from 0.24 ± 0.06 at P12 to 0.38 ± 0.12 at P13 (p < 0.05). The median total retinopathy score of 5.7 was significantly lower in eyes treated with Y27632 than controls (p < 0.001). Significant improvement was found in the specific categories of vascular tufts (p < 0.01) and extraretinal neovascularization (p < 0.05) in treated eyes. Those treated eyes also had a significantly decreased number of neovascular nuclei (p < 0.01).
These results suggest that Rho/Rho-kinase signaling pathways are involved in the early process of hypoxia-induced retinal neovascularization and Y27632 might have therapeutic potential for the treatment of retinal neovascularization.
Current eye research 11/2011; 36(11):1028-36. · 1.51 Impact Factor
-
Acta ophthalmologica 10/2009; · 2.44 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To assess the efficacy, duration of effect and safety of one intravitreal injection of bevacizumab in diabetic macular oedema (DMO).
Bevacizumab (1 mg/0.04 ml) was injected intravitreally into eyes with DMO (29 with and nine without previous treatments). Best corrected visual acuity (BCVA), intraocular pressure and central retinal thickness (CRT) were measured; slit-lamp examination, macular biomicroscopy, optical coherence tomography and fluorescein angiography were performed before and at 2-4, 8 and 12 weeks post-injection. Best corrected VA and CRT were analysed in both groups.
In the non-pretreated group, mean BCVA improved from 0.76 +/- 0.33 (baseline) to 0.57 +/- 0.30 and 0.54 +/- 0.27 at 2-4 weeks and 8 weeks post-injection, respectively (p = 0.02, p = 0.014, paired t-test). Mean CRT decreased from 632.4 +/- 196.0 microm (baseline) to 392.3 +/- 113.6 microm and 370.4 +/- 141.7 microm at the same time-points, respectively (p = 0.01, p = 0.01). There was no difference in BCVA or CRT at 12 weeks. In the pretreated group, mean BCVA improved from 0.62 +/- 0.30 (baseline) to 0.53 +/- 0.33 at 2-4 weeks post-injection (p = 0.01), and mean CRT decreased from 583.9 +/- 180.7 microm (baseline) to 404.1 +/- 197.9 microm at 2-4 weeks post-injection (p < 0.001). Mean BCVA was unchanged at 8 weeks and 12 weeks post-injection, although mean CRT remained lower at 8 weeks (p = 0.004). No ocular or systemic side-effects developed during follow-up.
One intravitreal injection of bevacizumab for DMO seems to be effective and safe in both eyes that have been treated previously and eyes that have not. The therapeutic effect is temporary and repeat treatment may be needed.
Acta ophthalmologica 06/2008; 86(7):800-5. · 2.44 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To determine the safety and efficacy of transsclerally placed intrapapillary wire microelectrodes implanted chronically into the optic nerve head of rabbit eyes.
Four platinum wire microelectrodes were passed through the sclera and implanted into the optic nerve head of five rabbit eyes for 4-6 months. Color fundus photography, fluorescein angiography, electroretinograms (ERGs), and visually evoked potentials (VEPs) were used to monitor the retina. Electrically evoked potentials (EEPs) were elicited by bipolar electrical stimulation of the optic nerve axons by different combinations of the four electrodes immediately after the implantation and at 1-month intervals thereafter. The effects of the chronic implantation of the electrodes on the morphology of the optic nerve were evaluated by histological and immunohistochemical examinations at 4 and 6 months after the implantation.
All of the electrodes remained stable in the implanted sites throughout the post-implantation period, except for one electrode that had pulled out of the optic nerve head at 1 month after implantation. No intraocular infection, inflammation, or vitreoretinal proliferation was observed in any eye. EEPs could be elicited from each pair of electrodes at all testing times. The mean threshold currents (charge densities) to evoke EEPs increased from 19.3 +/- 9.2 microA (6.0 +/- 2.9 microC/cm2) on the implantation day to 78.8 +/- 31.9 microA (24.6 +/- 10.0 microC/cm2) at 1 month after implantation, but did not change significantly thereafter. The implicit time and amplitude of the a- and b-waves of the ERGs and of P1 of the VEPs did not change significantly throughout the post-implantation period. Histological evaluation of the optic nerve head revealed slight tissue encapsulations surrounding the electrode and increased expression of glial fibrillary acidic protein near the surface of the optic nerve.
Implantation of transscleral intrapapillary microelectrodes appears to be safe and effective. These findings indicate that the implantation of microelectrodes in the optic nerve head should be considered for an optic nerve-based prosthesis.
Albrecht von Graæes Archiv für Ophthalmologie 04/2006; 244(3):364-75. · 2.17 Impact Factor
-
Xiaoyun Fang,
Hirokazu Sakaguchi,
Takashi Fujikado,
Makoto Osanai,
Hiroyuki Kanda,
Yasushi Ikuno,
Motohiro Kamei,
Masahito Ohji,
Dekang Gan,
Junsub Choi,
Tetsuya Yagi,
Yasuo Tano
[show abstract]
[hide abstract]
ABSTRACT: To determine whether wire microelectrodes implanted in the optic disc can be used to elicit cortical potentials.
Two or four platinum wire electrodes of two types, viz., the cut-end type and the exposed-tip type, were inserted through the vitreous and fixed in the optic disc of 16 rabbit eyes. Electrically evoked potentials (EEPs) were recorded after bipolar electrical stimulation with the two wire electrodes and by different combinations of the four-electrode system. The optic discs were examined histologically after the experiment.
The wire electrodes were successfully implanted and fixed into different positions of the optic disc without serious complications in all 16 eyes. EEPs could be elicited after bipolar electrical stimulation of the optic nerve using either the two-electrode system or different pairs of the four-electrode system. Threshold charge densities to elicit EEPs were 0.32-0.64 mC/cm(2) in eyes using the cut-end type of electrodes and 0.93-6.21 muC/cm(2) in eyes using the exposed-tip type. The amplitude of the EEPs increased with increasing electrical stimulus intensities. Histological evaluation revealed limited damage to the neural tissue adjacent to the electrode track.
The visual cortex can be activated by direct microelectrical stimulation of the optic nerve. The acute implantation of the wire microelectrodes into the optic disc by a transvitreal approach is feasible and results in only limited damage to the optic nerve.
Albrecht von Graæes Archiv für Ophthalmologie 02/2005; 243(1):49-56. · 2.17 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The purpose of this study was to assess the effects of vitrectomy on retinal function in macular and paramacular areas in patients with diabetic macular edema (DME). Ten eyes of 9 patients with successful vitrectomy for DME were evaluated by multifocal electroretinogram (mfERG), optical coherence tomography (OCT), and visual acuity preoperatively and 1, 2, 3, 4, 5 and 6 months postoperatively. Compared with pretreatment values, the response of the positive wave (P1) in macular and paramacular areas tended to decrease in latency from the second postoperative month, and increase in amplitude at the third postoperative month. There was no significant change in response of the negative wave (N1). The tendency in the change of macular function is coincident with that of macular morphology. Therefore, The multifocal ERG may provide objective criteria for the functional evaluation of DME before and after vitrectomy.
Documenta Ophthalmologica 10/2004; 109(2):131-7. · 2.11 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To determine the morphologic and functional changes of the fovea and retina of monkey eyes after macular translocation with 360-degree retinotomy.
Experimental study.
The retinas of eight monkey eyes were surgically translocated with a 360-degree retinotomy with procedures similar to those used on human eyes. At 1, 2, and 3 months after the surgery, the six eyes that had successful surgery were studied by light and transmission electron microscopy, terminal deoxynucleotidyl transferase (TdT)-dNTP terminal nick-end labeling (TUNEL) assay, and immunohistochemistry with peanut agglutinin (PNA) lectin and glial fibrillary acidic protein (GFAP). Retinal physiology was assessed by scotopic and photopic electroretinograms (ERGs).
The fovea was successfully translocated approximately 30 to 40 degrees superiorly in six eyes. The translocated macula and fovea had a normal layered architecture with no TUNEL-positive cells, minimal misalignment of the outer segments, and strong immunoreactivity to GFAP. The mean amplitudes of the scotopic and photopic b-waves were significantly reduced at 1 month after the surgery, and there was only a slight recovery at 3 months. No significant changes were observed in the mean implicit times after the surgery.
These findings indicate that macular translocation surgery with 360-degree retinotomy results in minimal morphologic alterations but significant depression of electrophysiologic function.
American Journal of Ophthalmology 07/2004; 137(6):1034-41. · 4.22 Impact Factor
-
Hirokazu Sakaguchi,
Takashi Fujikado,
Hiroyuki Kanda,
Makoto Osanai, Xiaoyun Fang,
Kazuaki Nakauchi,
Yasushi Ikuno,
Motohiro Kamei,
Masahito Ohji,
Tetsuya Yagi,
Yasuo Tano
[show abstract]
[hide abstract]
ABSTRACT: To investigate whether electrical stimulation of the optic nerve can elicit an electrical evoked potential (EEP) in rabbits and to determine whether such stimulation is a useful approach for the placement of a visual prosthesis.
Two needle-type electrodes were inserted into the optic nerve using a transvitreal approach. For electrical stimulation, monophasic and biphasic pulses were used. By stimulating the optic nerve, the EEP was elicited. After evaluation of the EEP, a histological study was carried out.
When electrical stimulation was applied, the EEP could be recorded. The threshold with monophasic and biphasic stimulation was 10 +/- 0 microA and 20 +/- 8.2 microA, respectively. Histological examination revealed no major complications, such as bleeding or degeneration, which might have resulted from the insertion of electrodes or the electrical stimulation.
Electrical stimulation of the optic nerve can elicit an EEP, suggesting that this approach may be useful for a visual prosthesis system.
Japanese Journal of Ophthalmology 48(6):552-7. · 0.92 Impact Factor
-
Hirokazu Sakaguchi,
Takashi Fujikado, Xiaoyun Fang,
Hiroyuki Kanda,
Makoto Osanai,
Kazuaki Nakauchi,
Yasushi Ikuno,
Motohiro Kamei,
Tohru Yagi,
Shigeru Nishimura,
Masahito Ohji,
Tetsuya Yagi,
Yasuo Tano
[show abstract]
[hide abstract]
ABSTRACT: Several approaches for placing an electrode device for visual prosthesis have been previously proposed. In this study, we investigated if transretinal stimulation from the suprachoroidal space can elicit an electrical evoked potential (EEP) in albino rabbits.
A flat electrode array (polyimide plate, platinum electrode) was developed and used for this study. After performing a scleral incision at 2-2.5 mm from the limbus and placing an anchoring suture, the array was inserted into the suprachoroidal space in the posterior portion of the eye by direct observation under a microscope. A platinum wire was implanted into the vitreous space as a reference electrode. For electrical stimulation, a biphasic pulse was used. When the electrode was stimulated, the EEP was recorded.
When the electrical stimulation from the suprachoroidal space was applied, the EEP could be recorded with an epidural electrode, and the threshold was 66.0 +/- 32.1 micro A (420 micro C/cm(2)) [corrected]. placement of the array and the electrical stimulation.
Transretinal electrical stimulation from the suprachoroidal space could elicit EEP, suggesting that this approach may be useful for a retinal prosthesis system.
Japanese Journal of Ophthalmology 48(3):256-61. · 0.92 Impact Factor
