Biomedical subjects

Takashi Fujikado

Publications and source records attributed to Takashi Fujikado.

At least 19 recordsLinked to original sources

PubMed2006

Allelic homogeneity in Avellino corneal dystrophy due to a founder effect.

Avellino corneal dystrophy (ACD) is a common corneal dystrophy that shows allelic homogeneity, R124H mutation in the transforming growth factor beta-induced (TGFBI) gene. There are distinct phenotypes of homozygous Avellino corneal dystrophy, termed types I and II. To investigate if the difference is caused by a modifier mutation, we sequenced the entire coding region of TGFBI of two types of ACDs. The sequences obtained from each type were identical, and we could not find any nucleotide alternations. Instead, we found seven single nucleotide polymorphisms (SNPs) compared with the normal control. Primer extension analysis revealed that all 14 homozygous patients were homozygotes in each SNP, which meant that all the patients shared the same disease haplotype. Subsequent analysis of 45 heterozygous ACD patients showed strong linkage disequilibrium between disease alleles of each SNP and ACD. These results strongly suggest that the allelic homogeneity of TGFBI associated corneal dystrophies (ACD, lattice corneal dystrophy types I and III, granular corneal dystrophy and Reis-Bucklers dystrophy) might not be caused by mutation hot spots but by the founder effects.

Alleles↗

PubMed2006

Inhibition of cyclooxygenase-2 expression by zinc-chelator in retinal ischemia.

The zinc ion (Zn2+) is abundant in neurons. However, excessive Zn2+ can induce neuronal cell death. This study examined the role of Zn2+ in transient retinal ischemia in adult male rats. The rats were sacrificed 4-24 h after retinal ischemia by high intra-ocular pressure, and the retinas were prepared for microscopic examination of retinal cell degeneration, and fluorescence microscopy using zinquin ethyl ester as the zinc ion-specific probe. Moreover, COX-2 expression was observed by Western blotting. In control retinas, there was a low Zn2+ concentration in the inner plexiform layer (IPL), a high Zn2+ concentration in the outer plexiform layer (OPL), and no detectable Zn2+ in either the ganglion cell layer (GCL) or the inner nuclear layer (INL). In contrast, in the retinas exposed to ischemia without the administration of the zinc ion chelators (Ca2+-EDTA and TPEN), Zn2+ deposits were found in the IPL and INL beginning 4 h after ischemia and degeneration of neurons was found in the GCL and INL. Less Zn2+ accumulation in the IPL and INL and less neuronal degeneration in the GCL and INL were found in the retinas treated with Ca2+-EDTA or TPEN before ischemia. Furthermore, the COX-2 protein levels increased 4-8 h after retinal ischemia, and chelation of zinc ion inhibited this effect. These results suggest that the accumulation of Zn2+ following an ischemic insult can cause retinal degeneration and induce abnormal COX-2 expression.

Animals↗

PubMed2006

Evaluation of residual retinal function by pupillary constrictions and phosphenes using transcorneal electrical stimulation in patients with retinal degeneration.

BACKGROUND: To evaluate inner-retinal function by pupillary constrictions and phosphenes evoked by transcorneal electrical stimulation (TES) in patients with hereditary retinal degeneration. METHODS: Consecutive 20 eyes of 20 patients (16 with retinitis pigmentosa (RP); and four with cone-rod dystrophy (CRD)) whose visual acuity was equal to or worse than 20/2000 at Osaka University Hospital and eight eyes of eight healthy subjects were enrolled. TES was performed on with a contact lens stimulating electrode. The electrically evoked pupillary response (EEPR) was recorded by a pupillometer, and the phosphenes by the subjective responses. Three electrical current thresholds were determined: T1, threshold current for initial phosphene; T2, threshold for eliciting a phosphene extending into the central field; and P, threshold for a relative pupillary constriction > or = 3%. The EEPR and phosphene thresholds were compared with the visual acuity or the visual field. RESULTS: All T1, T2 and P were significantly higher in patients than in normals (Mann-Whitney, P<0.001). Both T1 and T2 were not correlated with visual acuity but depended on the area and location of the residual visual field. T1 and T2 in RP eyes with a EEPR was significantly lower than that in RP eyes without an EEPR. During TES, all subjects and patients had no pain, and no complications except for a slight corneal superficial punctuate keratopathy. CONCLUSIONS: The safety and the efficacy of TES to estimate the residual inner-retinal function in patients with retinal degeneration indicate that TES can be used as one of the most important test to select candidates for retinal prostheses.

Adult↗

PubMed2006

Wavefront analysis of eye with monocular diplopia and cortical cataract.

PURPOSE: To determine whether higher-order aberrations can explain the monocular diplopia reported by a patient. DESIGN: Observational case report. METHODS: A patient complaining of monocular diplopia was examined with the Hartmann-Shack aberrometer to determine if the higher-order wavefront aberrations could account for the diplopia. The patient had a mild cortical cataract, and measurements were made before and after lensectomy. In addition, the retinal image was simulated using Zernike polynomials. RESULTS: Spherical aberration (0.20 microm for 4-mm pupil) and secondary astigmatism (-0.12 microm) were increased in the eye. The simulated retinal image had a double configuration that was approximately the same as the subjective image reported by the patient. After cataract surgery, the diplopia disappeared, and the spherical aberrations and secondary astigmatism were considerably decreased. CONCLUSIONS: The monocular diplopia probably stemmed from the combined effects of spherical aberration and secondary astigmatism caused by the cortical cataract.

Adult↗

PubMed2006

Paradoxical increase of visual impairment with punctal occlusion in a patient with mild dry eye.

We report a paradoxical increase in visual impairment after punctal plug placement despite improvement in corneal epithelial damage caused by mild dry eye. Ocular higher-order aberrations (HOAs) were measured sequentially with a wavefront sensor before and after punctal plug insertion in a patient with mild dry eye. Although postblink HOAs tend to increase in normal subjects or patients with dry eye, after treatment there was a maximum spike in HOAs for a few seconds that decreased gradually. Excessive retention of tear film by punctal occlusion may cause inferosuperior asymmetrical distribution in precorneal tear-film thickness, possibly leading to slower wavefront on the inferior cornea and increased coma-like aberrations. Increased visual impairment might occur paradoxically despite improvement in the corneal epithelial damage caused by dry eye.

Adult↗

PubMed2006

Wavefront analysis of eyes with cataracts in patients with monocular triplopia.

PURPOSE: To determine whether wavefront analysis using a Hartmann-Shack (H-S) aberrometer can reveal the cause of monocular triplopia in eyes with mild cataracts. METHODS: Six patients (nine eyes; age range 38-58 years; average 49.8 +/- 6.9 years) who complained of monocular triplopia at the Osaka University Hospital between January and December 2003 were examined. Wavefront analyses of ocular and corneal aberrations of the central 4 mm diameter were performed using a H-S aberrometer equipped with a Placido ring videokeratoscope. The ocular and corneal higher-order wavefronts were fitted with a fourth-order Zernike expansion. RESULTS: All nine eyes showed mild nuclear cataract and had a mean spherical refractive error of -10.3 +/- 3.5 D. The visual acuity was > or = 20/40 except in one eye with glaucoma. For the Zernike polynomials, the trefoil aberration (C3-3) and the spherical aberration (C40) were significantly higher than those of age-matched normal controls (p < 0.001). The simulated retinal image of a Landolt C showed that the combination of trefoil aberration and the spherical aberration can cause an image with a triple configuration. CONCLUSIONS: Monocular triplopia was reported by middle-aged patients with mild nuclear cataract and high myopia. Wavefront analyses suggested that the triple configuration was caused by the combined increase of the trefoil and spherical aberration in lenses with mild nuclear cataracts.

Adult↗

PubMed2006

Serial measurements of higher-order aberrations after blinking in normal subjects.

PURPOSE: To investigate sequential changes in the optical quality of normal eyes associated with blinking. METHODS: Ocular higher-order aberrations (HOAs) were measured sequentially by using a wavefront sensor for 30 seconds in 20 eyes of 20 normal subjects. During the measurement, subjects were forced to blink every 10 seconds. The obtained aberration data were analyzed in the central 4-mm diameter for coma-like, spherical-like, and total HOAs up to the sixth-order Zernike polynomials. RESULTS: The serial changes in the HOAs with blinking were classified into four groups by pattern: stable (25%), small-fluctuation (45%), sawtooth (20%), and others (10%). In the subjects with the sawtooth pattern, the total HOAs increased significantly (P < 0.001, one-way repeated-measures ANOVA) with time between blinks. Increased total HOAs and coma-like aberrations in the subjects with the sawtooth pattern suggested that the inferosuperior asymmetric change in tear film thickness is responsible. CONCLUSIONS: Dynamic changes in HOAs after blinking showed variations even in clinically normal subjects. Serial measurements of HOAs may be useful in evaluating the dynamic changes in tear film and the effects on the quality of vision after blinking.

Adult↗

PubMed2006

Ptf1a determines horizontal and amacrine cell fates during mouse retinal development.

The vertebrate neural retina comprises six classes of neurons and one class of glial cells, all derived from a population of multipotent progenitors. There is little information on the molecular mechanisms governing the specification of cell type identity from multipotent progenitors in the developing retina. We report that Ptf1a, a basic-helix-loop-helix (bHLH) transcription factor, is transiently expressed by post-mitotic precursors in the developing mouse retina. Recombination-based lineage tracing analysis in vivo revealed that Ptf1a expression marks retinal precursors with competence to exclusively produce horizontal and amacrine neurons. Inactivation of Ptf1a leads to a fate-switch in these precursors that causes them to adopt a ganglion cell fate. This mis-specification of neurons results in a complete loss of horizontal cells, a profound decrease of amacrine cells and an increase in ganglion cells. Furthermore, we identify Ptf1a as a primary downstream target for Foxn4, a forkhead transcription factor involved in the genesis of horizontal and amacrine neurons. These data, together with the previous findings on Foxn4, provide a model in which the Foxn4-Ptf1a pathway plays a central role in directing the differentiation of retinal progenitors towards horizontal and amacrine cell fates.

Amacrine Cells↗

PubMed2005

Electrophysiological and histological studies of chronically implanted intrapapillary microelectrodes in rabbit eyes.

PURPOSE: To determine the safety and efficacy of transsclerally placed intrapapillary wire microelectrodes implanted chronically into the optic nerve head of rabbit eyes. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Animals↗

PubMed2005

Transcorneal electrical stimulation rescues axotomized retinal ganglion cells by activating endogenous retinal IGF-1 system.

PURPOSE: To investigate the effect of transcorneal electrical stimulation (TES) on the survival of axotomized RGCs and the mechanism underlying the TES-induced neuroprotection in vivo. METHODS: Adult male Wistar rats received TES after optic nerve (ON) transection. Seven days after the ON transection, the density of the surviving RGCs was determined, to evaluate the neuroprotective effect of TES. The levels of the mRNA and protein of insulin-like growth factor (IGF)-1 in the retina after TES were determined by RT-PCR and Northern and Western blot analyses. The localization of IGF-1 protein in the retina was examined by immunohistochemistry. RESULTS: TES after ON transection increased the survival of axotomized RGCs in vivo, and the degree of rescue depended on the strength of the electric charge. RT-PCR and Northern and Western blot analyses revealed a gradual upregulation of intrinsic IGF-1 in the retina after TES. Immunohistochemical analysis showed that IGF-1 immunoreactivity was localized initially in the endfeet of Muller cells and then diffused into the inner retina. CONCLUSIONS: TES can rescue the axotomized RGCs by increasing the level of IGF-1 production by Muller cells. These findings provide a new therapeutic approach to prevent or delay the degeneration of retinal neurons without the administration of exogenous neurotrophic factors.

Animals↗

PubMed2004

Transretinal electrical stimulation by an intrascleral multichannel electrode array in rabbit eyes.

BACKGROUND: A new method of stimulating the retina electrically, called suprachoroidal transretinal stimulation (STS), was shown to be effective in eliciting electrically evoked cortical potentials (EEPs) in Royal College of Surgeons (RCS) rats. Before extending this technique to patients, it is important to determine its safety and feasibility in eliciting EEPs from medium-size animal (rabbits). The purpose of this study was to determine the safety and efficacy of the surgical procedures used to implant an multichannel electrode array into a scleral pocket, and to determine whether the implanted electrodes can stimulate the retina effectively. METHODS: These acute experiments were conducted on six rabbits. An array of eight gold microelectrodes, embedded in polyimide, was implanted into a scleral pocket over the visual streak area. The size of the microarray was 2 x 4 x 0.180 mm. The reference electrode was implanted into the vitreous. The electrode array and reference electrodes were connected to a stimulator to deliver monophasic current pulses. Cortical responses were recorded with a stainless steel electrode implanted into each rabbit's skull over the visual cortex. After the experiment, the eyes and electrodes were examined histologically. RESULTS: The surgical procedures for electrode implantation were accomplished without serious complications. EEPs were recorded after monophasic electrical pulse stimulation from each electrode. The mean threshold for EEPs was 55.0+/-10.0 microA with a 0.5-ms duration inward current pulse. The charge delivered at threshold was about 27.5 nC, and the charge density was about 56.0 microC/cm2. Histopathological examination of the retinal tissue around the area of stimulation did not show damage at the light microscope level with the electrical parameters used. CONCLUSIONS: Our technique for STS with an intrascleral microelectrode array is safe in rabbit eyes, and EEPs were elicited by current densities that did not induce tissue damage. These results suggest that STS via intrascleral multichannel electrodes is a feasible method for stimulating the retina.

Animals↗

PubMed2004

Direct stimulation of optic nerve by electrodes implanted in optic disc of rabbit eyes.

PURPOSE: To determine whether wire microelectrodes implanted in the optic disc can be used to elicit cortical potentials. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Animals↗

PubMed2004

Vitrectomy and internal limiting membrane peeling for myopic foveoschisis.

PURPOSE: Myopic foveoschisis is common in high myopia. We report results of a pilot study of vitrectomy for patients with myopic foveoschisis. DESIGN: Interventional case series. METHODS: In an institutional setting five patients with high myopia (six eyes), and who had progressive visual impairment presumably due to myopic foveoschisis were studied. No eyes had a macular hole preoperatively based on optical coherence tomography (OCT). We performed vitrectomy including vitreous cortex removal, internal limiting membrane (ILM) peeling, and gas tamponade. Patients were followed for at least 6 months. Best-corrected visual acuity (BCVA), OCT. Scanning laser ophthalmoscope (SLO) microperimetry was examined in three eyes. RESULTS: The foveal detachment resolved completely in five eyes and partially in one eye. No serious complications developed including macular hole formation or retinal detachment; BCVA improved more than two lines in all eyes (100%) 6 months postoperatively (P <.01); SLO microperimetry showed smaller scotoma compared with preoperatively and stabilized fixation. CONCLUSIONS: Vitrectomy with vitreous cortex removal, ILM peeling, and gas tamponade could be useful to treat myopic foveoschisis in highly myopic eyes. Because the natural course of the disease is not well-understood, further study should establish indications for this surgery.

Basement Membrane↗

PubMed2004

Retinal changes after macular translocation with 360-degree retinotomy in monkey eyes.

PURPOSE: To determine the morphologic and functional changes of the fovea and retina of monkey eyes after macular translocation with 360-degree retinotomy. DESIGN: Experimental study. METHODS: 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). RESULTS: 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. CONCLUSION: These findings indicate that macular translocation surgery with 360-degree retinotomy results in minimal morphologic alterations but significant depression of electrophysiologic function.

Animals↗

PubMed2004

Age-related changes in ocular and corneal aberrations.

PURPOSE: To compare the ocular and corneal higher-order aberrations (HA) in eyes of different ages. DESIGN: Observational cross-sectional study. METHODS: Sixty-six eyes of 66 normal subjects (age range 4-69 years; average 37.4 +/- 15.4 years) were examined. Wavefront aberrations of the whole eye (ocular) and cornea were measured for the central 4 mm using a Hartmann-Shack aberrometer. RESULTS: Ocular Coma-like aberration (r = 0.270, P =.029), Spherical-like aberration (r = 0.531, P =.001), and total HA(r = 0.431, P =.001) were significantly correlated with age, whereas the corneal aberrations were not significantly correlated. The ocular total HA aberrations increased significantly after age 50 years. CONCLUSIONS: After 50 years of age, ocular aberrations increased abruptly due to the increase of lenticular HA. Customized ablation should be carefully considered, especially in eyes of presbyopic age.

Adolescent↗

PubMed2004

Light scattering and optical aberrations as objective parameters to predict visual deterioration in eyes with cataracts.

PURPOSE: To predict the visual deterioration of eyes with cortical (CC) or nuclear (NC) cataract from objective data on ocular higher-order aberration (HOA) and forward (FLS) and backward light scattering (BLS). SETTING: Osaka University Medical School, Osaka, Japan. METHODS: Twenty-two eyes with mild NC, 41 eyes with mild CC, and 11 normal eyes were examined. Higher-order aberrations were calculated with the Zernike polynomials up to the fourth order from the values obtained by wavefront analysis using the Hartmann-Shack aberrometer. Forward light scattering was calculated from the size of the aberrometer spot images for the central 4 mm, and backward light scattering (BLS) was calculated from the optical density of the Scheimpflug images. The relationship between the area under the log contrast sensitivity function (AULCSF) curve and HOAs, FLS, and BLS was examined. RESULTS: Area under the log contrast sensitivity function was moderately correlated with the HOAs, FLS, and BLS. Multiple linear regression analysis revealed that the AULCSF was predicted by the linear combination of these variables (R(2)=.484, P<.001). Area under the log contrast sensitivity was predicted by BLS and HOA (R(2)=.555) in the NC group and by FLS and HOAs (R(2)=.540) in the CC group. CONCLUSIONS: Loss of contrast sensitivity was predominantly due to BLS and HOA in eyes with NC and FLS and HOA in eyes with CC. Higher-order aberrations, FLS, and BLS, variables that are obtained objectively, can be used to predict quantitatively the visual deterioration in cataractous eyes.

Adult↗

PubMed2004

Wavefront analysis of an eye with monocular triplopia and nuclear cataract.

PURPOSE: To determine whether higher-order aberrations explain patient-reported monocular triplopia. DESIGN: Observational case report. METHOD: A patient complaining of monocular triplopia was examined with a Hartmann-Shack aberrometer to determine whether higher-order wavefront aberrations could account for the triplopia. The patient had a mild nuclear cataract; measurements were made before and after lensectomy. The retinal image was simulated using the Zernike polynomials. RESULT: Spherical aberration (-0.18 microm, 4 mm pupil) and trefoil aberration (-0.16 microm) were increased. The simulated retinal image had a triple configuration similar to the subjective image reported by the patient. After cataract surgery, the subjective triplopia disappeared; spherical, and trefoil aberrations were markedly decreased. CONCLUSION: The monocular triplopia probably stemmed from combined effects of spherical and trefoil aberrations caused by the nuclear cataract.

Adult↗

PubMed2004

Macular translocation surgery and retinal circulation times.

PURPOSE: To quantify and compare the retinal circulation times before and after macular translocation surgery. METHODS: In nine patients undergoing macular translocation with 360-degree retinotomy, arm-retina and arteriovenous passage times were quantified from preoperative and postoperative scanning laser fluorescein angiograms. A control group of eight patients who had not undergone any intraocular surgery was also evaluated. The time that between injection into the antecubital vein and the appearance of fluorescein at two selected points on superotemporal and inferotemporal arteries near the disk provided the arm-retina time. For the arteriovenous passage time, 50% of the maximal fluorescence time difference was assessed from the intensity curves of arteries and corresponding veins at the same points for the arm-retina time. Postoperative measurements were obtained an average of 10.6 months after surgery. RESULTS: No significant difference was noted between preoperative and postoperative values of the arm-retina time (mean +/- SD: 14.41 +/- 2.73 seconds versus 14.67 +/- 3.85 seconds, respectively; P = 0.84) or that of the arteriovenous passage time (2.66 +/- 0.74 seconds versus 2.47 +/- 0.68 seconds, respectively; P = 0.37) in the study group. The arm-retina time (14.96 +/- 2.01 seconds) and arteriovenous passage time (2.44 +/- 0.68 seconds) in the control group did not differ from preoperative and postoperative arm-retina times (P = 0.65 and P = 0.85) and arteriovenous passage times (P = 0.54 and P = 0.93) in the study group. The arteriovenous passage time correlated with the degree of retinal rotation around the optic disk in the study group (r = -0.70; P = 0.04). CONCLUSION: Macular translocation surgery does not alter retinal macrocirculation in the long term.

Aged↗