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Biomedical subjects

Shigeki Machida

Publications and source records attributed to Shigeki Machida.

15 recordsLinked to original sources

Protective effect of hepatocyte growth factor against degeneration of the retinal pigment epithelium and photoreceptor in sodium iodate-injected rats.

PURPOSE: To investigate the possible protective effect of hepatocyte growth factor (HGF) against degeneration of photoreceptors and retinal pigment epithelium (RPE) in vivo. METHODS: Sprague-Dawley (SD) rats received an intravitreal injection of HGF in the right eye. The left eye was injected with vehicle as a control. Two days after the intravitreal injections, rats were administered 40 mg/kg of sodium iodate (NaIO3) intravenously. Scotopic ERGs were elicited by different stimulus intensities with a maximum luminance of 0.84 log cds/m2. To evaluate RPE function, the azide response was evoked by intravenous injection of 0.1 mg sodium azide. These electrophysiological measurements were conducted on days 4, 7, 14, and 28 after the NaIO3 injections. After recording ERGs or azide response, animals were sacrificed for quantification of the histological change and immunohistochemical analysis using antibodies against RPE 65. RESULTS: The threshold for the scotopic b-wave was significantly lower in HGF-treated eyes than in untreated control eyes (p < 0.005), and maximum b-wave amplitudes (Vbmax) were significantly larger in HGF-treated eyes (p < 0.05) across all experimental time points after NaIO3 injection. Azide response amplitudes were significantly larger in the HGF-treated eyes than in the untreated eyes (p < 0.05). The structure of the outer retina was preserved to a greater degree in the HGF-treated eyes than in the untreated eyes (p < 0.05). Immunohistochemical analysis demonstrated that irregular alignment of the outer nuclear layer was confined to the retinal area that was not stained with RPE 65. CONCLUSIONS: Our results indicated that an intravitreal injection of HGF provided significant protection against degeneration of the photoreceptor and RPE induced by systemic administration of NaIO3. This suggests that HGF could be used as a therapeutic agent for degeneration of photoreceptors as well as RPE.

Animals↗

High prevalence of myopia in Japanese patients with idiopathic focal subretinal neovascularization.

PURPOSE: To determine whether myopia is more prevalent in Japanese patients with idiopathic focal subretinal neovascularization (IFSN) than in normal control subjects. METHODS: Forty-seven eyes of 46 patients with an initial diagnosis of IFSN and 291 eyes of 291 controls were studied. Refractive errors were measured with an autorefractometer, and the spherical equivalent of the refractive error was used for the statistical analyses. All patients had undergone fluorescein angiography (FA) to confirm the presence of the choroidal neovascularization. In addition, indocyanine green angiography (ICGA) had been performed to determine whether chorioretinal atrophy and breaks of Bruch's membrane, which are consistent with myopic retinopathy, were present. RESULTS: The mean age of the patients in the control group was not significantly different from that of patients in the IFSN group. The mean spherical equivalent of the refractive errors was -2.62 +/- 2.70 diopters (D) in the control group and -5.24 +/- 3.41 D in the IFSN group (P = 0.00005). The incidence of high myopia was significantly higher in the IFSN group (41.3%) than in the control group (12.0%, P < 0.0001). FA and ICGA showed no chorioretinal atrophy and lacquer cracks, thus confirming that patients with myopic retinopathy were excluded from the IFSN group. During the mean follow-up period (44.7 months), myopic retinopathy did not develop in any of the eyes in the IFSN group. CONCLUSION: Japanese patients with IFSN were highly myopic, suggesting that myopia may play a role in the development of choroidal neovascularization in IFSN patients.

Adolescent↗

Third-order neuronal responses contribute to shaping the negative electroretinogram in sodium iodate-treated rats.

PURPOSE: To determine possible mechanisms that shape the negative electroretinograms (ERGs) in rats with photoreceptor degeneration induced by destruction of the retinal pigment epithelium. METHODS: Sprague-Dawley rats (n = 48) were injected intravenously with 60 mg/kg of sodium iodate (NaIO(3)). Full-field ERGs were elicited by different stimulus intensities with a maximum luminance of 1.23 log cd-s/m(2) and recorded at 6 hr and on days 7, 14, and 28 after the NaIO(3) injections. DL-2-amino-4-phosphonobutyric acid (APB, 1 mM) or N-methyl-L-aspartic acid (NMDA, 5 mM) was injected into the vitreous cavity to isolate photoreceptor (PIII), second-order, and third-order neuronal responses. After recording the ERGs, animals were sacrificed for histological analysis. RESULTS: Negative ERGs were recorded under scotopic conditions on day 7 after the NaIO(3) injection. An intravitreal injection of NMDA eliminated most of the a-wave, resulting in the abolition of the negative ERG. On days 14 and 28, the a-wave amplitudes were reduced compared to those on day 7 with the loss of the negative ERGs. The mean amplitudes of the PIII and second-order neuronal responses were progressively reduced until day 7. In contrast, the mean amplitude of the third-order neuronal responses were relatively well-preserved until day 7 and then were decreased between days 7 and 14. As a result, the amplitude of the third-order neuronal response dominated over the second-order neuronal response on day 7. There was no significant difference in the middle and inner retinal morphology at each time point. CONCLUSIONS: NaIO(3) produced negative ERGs transiently, and the third-order neuronal responses were the main contributors to the negative ERG. The relative preservation of the third-order neuronal response plays a role in shaping the negative ERGs in this model.

Animals↗

Functional changes in rod and cone pathways after photoreceptor loss in light-damaged rats.

PURPOSE: To determine the functional changes in the rod and cone pathways after photoreceptor loss by continuous light exposure. METHODS: Fifty-four male Sprague-Dawley rats were exposed to diffuse fluorescent light of 2000 lux for 24 or 48 hr. Two weeks after the light exposure, full-field scotopic and photopic electroretinograms (ERGs) were elicited by different stimulus intensities with a maximum luminance of 0.84 log cd-s/m2. The amplitudes of the a- and b-waves of the scotopic ERGs and the b-wave of the photopic ERGs were measured. The animals were sacrificed after the ERG recordings, and the number of surviving rod and cone nuclei in the outer nuclear layer was counted. RESULTS: The logarithm (log) of the amplitudes of the maximum rod a-wave (rod Va(max)) and b-wave (rod Vb(max)) was reduced monotonically with a decrease in the rod nucleus counts (p < 0.0001). The regression line for the rod Va(max) decrease was significantly steeper than that for the rod Vb(max) (p < 0.005). The maximum b-wave amplitudes of the photopic ERGs (cone Vb(max)) were significantly correlated with the number of cone nuclei in a log-linear fashion. The slopes of the regression lines for the rod Vb(max) and cone Vb(max) were 0.0067 and 0.0140, respectively, which indicates that the amplitude of the cone b-wave was more severely affected than that of the rod b-waves by light-induced photoreceptor degeneration (p < 0.005). CONCLUSIONS: The amplitudes of the rod and cone ERGs were correlated with rod and cone nuclei counts in a log-linear fashion in light-damaged rats. The functional loss from the photoreceptor death had a greater effect on the cone pathway than on the rod pathway when the retinal function was assessed by the b-wave.

Animals↗

Selective loss of the photopic negative response in patients with optic nerve atrophy.

OBJECTIVE: To determine how the photopic negative response (PhNR) is altered in patients with optic nerve atrophy. METHODS: Ten patients with optic nerve atrophy induced by compression, trauma, or inflammation were examined. There were 6 men and 4 women with a mean age of 52.4 years. Ten age-matched control subjects were examined with the same protocol. Full-field electroretinograms were recorded, and the retinal nerve fiber layer thickness surrounding the optic nerve head was measured by means of optical coherence tomography. RESULTS: The amplitudes of the rod, maximum, cone, and 30-Hz flicker electroretinograms of the affected eyes were not different from those of the corresponding waves of the contralateral unaffected eyes or control eyes. In contrast, the amplitude of the PhNR was significantly smaller in the affected eyes than in the contralateral (P =.005) or control (P<.001) eyes. The decrease in amplitude of the PhNR preceded thinning of the retinal nerve fiber layer. There was a significant correlation between the PhNR amplitude and retinal nerve fiber layer thickness in eyes with optic nerve atrophy (r = 0.879; P<.001). CONCLUSIONS: Selective reduction and loss of the PhNR amplitude was found in eyes with optic nerve atrophy, which suggests that the PhNR can be used to evaluate the function of ganglion cells or their axons.

Adult↗

Predominant loss of the photopic negative response in central retinal artery occlusion.

PURPOSE: To determine how the photopic negative response (PhNR) is affected in central retinal artery occlusion (CRAO). DESIGN: Observational case series. METHODS: Seven patients with unilateral CRAO were included. Full-field scotopic and photopic electroretinograms (ERGs) including the PhNR were recorded. Each ERG amplitude in the affected eye was expressed as a percentage of amplitude of the corresponding wave in the unaffected eye. RESULTS: Mean of the PhNR amplitude was reduced to 12.3 +/- 11.7% of that of unaffected eyes whereas the cone b-wave amplitude was attenuated to only 73.4 +/- 30.4%. This reduction of the PhNR amplitude was more significant than that of other waves including the rod b-wave, maximum a-wave and b-wave, cone a-wave and b-wave, and 30 Hz flicker ERG (P <.005). CONCLUSIONS: The PhNR was severely affected in CRAO despite relative preservation of the cone b-wave, implicating massive loss of ganglion cells and their axons.

Aged↗

Decrease of blue cone sensitivity in acute idiopathic blind spot enlargement syndrome.

PURPOSE: To determine the sensitivity of the blue cone system by static perimetry in patients with unilateral acute idiopathic blind spot enlargement (AIBSE) syndrome. DESIGN: Observational case series. METHODS: Four patients with AIBSE syndrome, aged 16 to 30 years, were studied. Diagnosis of the AIBSE syndrome was based on clinical findings including an enlarged blind spot without corresponding ophthalmoscopic changes of the ocular fundus and with depressed multifocal electoretinograms. The visual sensitivity and mean deviations (MD) were measured by white-on-white (W/W) and blue-on-yellow (B/Y) automated perimetry. RESULTS: The average difference in the MD between the affected and unaffected eyes was 4.87 +/- 1.51 dB and 13.65 +/- 4.19 dB for W/W and B/Y perimetries, respectively. The difference between the two groups of eyes was significantly greater for B/Y perimetry than that for W/W perimetry (P =.01). CONCLUSIONS: Our results suggest that the decrease of blue cone sensitivity is diffusely present over the retina in eyes with AIBSE syndrome. We recommend B/Y perimetry as a sensitive measure to detect retinal dysfunction that is not detected by W/W perimetry.

Acute Disease↗

Correlation of retinal function with retinal histopathology following ischemia-reperfusion in rat eyes.

PURPOSE: To investigate the relationship between retinal function and histopathology following retinal ischemia-reperfusion in rats. METHODS: Retinal ischemia was induced in 27 Sprague-Dawley rats by raising the intraocular pressure for 60- or 90-minutes. Two weeks after the retinal ischemia-reperfusion, ganzfeld stimuli of different luminances (maximum 0.51 log cd-s/m2) were used to elicit full-field ERGs from the right (experimental) and left (control) eyes. The amplitudes of the scotopic b-waves were measured, and intensity-response curves were plotted. The b-wave amplitudes at the initial peak (VbIP), the dip (Vb(dip)), and the maximum stimulus intensity (Vb(max)) were measured. The animals were sacrificed after the ERG recordings to determine the surviving retinal cells in the inner nuclear layer (INL). RESULTS: The log values of the VbIP, Vb(dip) and Vb(max) were linearly correlated with the number of surviving cells in the INL (r = 0.928, 0.905, and 0.913 for VbIP, Vb(dip) and Vb(max), respectively; p < 0.0001 for each). The slope of the regression line for the Vb(dip) was significantly steeper than that for the VbIP and Vb(max) (p < 0.005). The regression line for the Vb(dip) reached undetectable level of the b-wave (<1 microV) even though approximately 25% of the cells still remained in the INL. CONCLUSIONS: The amplitude of the scotopic b-wave is a sensitive index of the surviving INL cells. However, if one selects the stimulus intensity at the dip, the functional loss would be exaggerated in spite of the presence of cells in the INL.

Animals↗

Neuroprotective effect of hepatocyte growth factor against photoreceptor degeneration in rats.

PURPOSE: To determine whether hepatocyte growth factor (HGF) has a neuroprotective effect against photoreceptor degeneration in rats. METHODS: Eight-week-old Sprague-Dawley (SD) and 24-day-old Royal College of Surgeons (RCS) rats received an intravitreal injection of HGF in the right eyes. The left eyes were injected with vehicle and served as the control. Two days after the injections, the SD rats were exposed to fluorescent light of 3000 lux for 72 hours. Scotopic and photopic electroretinograms (ERGs) were recorded 2 weeks after the light damage and at 70 days of age in RCS rats. After the ERG recordings, the animals were killed for histologic analysis. Some RCS rats were killed at 2 weeks after HGF-treatment for TdT-dUTP terminal nick-end labeling (TUNEL) studies. RESULTS: In both light-damaged and RCS rats, the thresholds for the scotopic and photopic b-wave were significantly lower in the HGF-treated eyes than in the control eyes (P <0.02). The maximum b-wave amplitudes (Vbmax) of the scotopic and photopic ERGs were significantly larger in the HGF-treated eyes (P <0.0005) with a significantly greater number of photoreceptor nuclei than in the control eyes in both animal models (P <0.005). The vehicle-injected eyes of RCS rats had significantly larger numbers of TUNEL-positive photoreceptor nuclei than the HGF-treated eyes (P=0.005). CONCLUSIONS: Intravitreal HGF led to the morphologic and physiological preservation of photoreceptors in rats with photoreceptor degeneration induced by phototoxicity or a gene mutation. The antiapoptotic effect may be the mechanism for the neuroprotective action of HGF.

Animals↗

Observation of the ocular fundus by an infrared-sensitive video camera after vitreoretinal surgery assisted by indocyanine green.

PURPOSE: To investigate how long indocyanine green (ICG) dye remains in the ocular fundus and how the remaining dye interferes with ICG angiographic findings after vitreoretinal surgery assisted by ICG. METHODS: Eight eyes with macular hole, three with epiretinal membrane, and one with an intraocular foreign body were included. Those patients underwent vitrectomy facilitated by an intraocular administration of ICG. An infrared sensitive video camera was used to take fundus pictures pre- and postoperatively. In 2 of 12 cases, the authors performed ICG angiography at 2 weeks and at 3 months after the surgery. RESULTS: At 1 month after surgery, diffuse hyperfluorescence was observed throughout the posterior pole of the ocular fundus in all cases. The area where macular hole existed before the surgeries revealed hyperfluorescence in 6 of 8 eyes with macular hole (75%). These hyperfluorescent findings became less prominent with time postoperatively, while optic disk hyperfluorescence persisted for 12 months in all cases. In the early phase of ICG angiography at 2 weeks postoperatively, the retinal and choroidal circulation could be depicted. However, in the middle phase the choroidal veins were hardly visible. The angiographic pictures of the late phase mimicked those seen without intravascular administration of ICG. Even at 3 months after surgery, the optic nerve head revealed hyperfluorescence in the middle and late phases. CONCLUSIONS: The residual ICG in the ocular fundus produced prolonged hyperfluorescence after surgery. This abnormal condition affected ICG angiographic findings in the middle and late phases.

Adult↗

Choroidal circulatory disturbance in ocular sarcoidosis without the appearance of retinal lesions or loss of visual function.

BACKGROUND: Birdshot chorioretinopathy, acute posterior multifocal placoid pigment epitheliopathy, and retinal pigment epithelial detachment have been reported as rare manifestations associated with sarcoidosis, suggesting that ocular sarcoidosis may affect the choroidal circulation. We report a case of ocular sarcoidosis representing a choroidal circulatory disturbance without the appearance of retinal lesions or loss of retinal function. CASE: A 20-year-old woman was referred with blurred vision in the left eye. Inflammatory change in the anterior segment of the eye was noted with multiple nodules on the iris. OBSERVATIONS: Hematological examination revealed elevated lysozyme levels. Bilateral hilar lymphadenopathy was noted on chest X-ray. Specimens obtained by transbronchial lung biopsy revealed granuloma with Langhans giant cells, which led to the diagnosis of sarcoidosis. The eye was treated with topical steroid. The symptoms and the inflammatory change in the anterior segment disappeared within 10 days. However, despite the normal appearance of the ocular fundus, fluorescein angiography revealed multiple puncta of hyperfluorescence. In indocyanine green angiography, a filling delay was noted in the area corresponding to the punctate lesions. Static visual field testing and multifocal electroretinography showed no significant changes. At the last visit, 15 months after the left eye became asymptomatic, the choroidal lesions had disappeared with no residual alteration of the funduscopic appearance or visual function. CONCLUSIONS: This case indicates that choroidal circulatory disturbance can underlie ocular sarcoidosis even in the absence of funduscopically detectable lesions and loss of visual function.

Adult↗

Relationship between the s-wave amplitude of the multifocal electroretinogram and the retinal nerve fiber layer thickness in glaucomatous eyes.

PURPOSE: To determine whether a significant correlation exists between the amplitude of the s wave of the multifocal electroretinogram (mfERG) and the retinal nerve fiber layer thickness (RNFLT) in glaucomatous eyes. METHODS: Twenty-three eyes of 23 patients with glaucoma were studied. In all eyes, the severity of the defects in the upper visual field differed significantly from the severity of those in the lower half. Patients having visual field halves with mean deviation (MD) values lower than -5 dB were placed in group A, and patients having visual field halves with MD values greater than -5 dB were placed in group B. The mfERGs were elicited by 37 stimulus elements alternating from white to black in a pseudorandom binary m-sequence at a frequency of 9.4 Hz. The mfERGs in the upper and lower visual field halves were summed to yield upper and lower averaged waves. The GDx variable corneal compensator and optical coherence tomography were used to measure the RNFLT. RESULTS: The retinal nerve fiber layer was significantly thinner in group A than in group B. There was a significant correlation between the RNFLT and the MD values of visual field defects. The s-wave amplitude was significantly smaller in group A than in group B. The s-wave amplitude also correlated significantly with the MD and the RNFLT. CONCLUSION: The significant correlations between the s-wave amplitude and the MD, and between the s-wave amplitude and the RNFLT, indicate that the s-wave receives significant contributions from the retinal ganglion cells and their axons.

Aged↗

Changes of oscillatory potentials and photopic negative response in patients with early diabetic retinopathy.

PURPOSE: To investigate the clinical significance of the oscillatory potentials (OPs) and photopic negative response (PhNR) of the electroretinogram (ERG) in patients with early diabetic retinopathy. METHODS: One hundred two diabetic patients with diabetic retinopathy at different stages were examined. Thirty-two age-matched normal controls were also studied. Full-field maximal and photopic cone ERGs were recorded. The amplitudes and implicit times of the OPs, cone b wave, and PhNR were compared at the different stages of diabetic retinopathy. RESULTS: The a and b wave amplitudes of the maximal scotopic ERGs remained unchanged despite advancing stages of retinopathy, but the OP amplitudes were significantly attenuated even at an early stage of diabetic retinopathy. The amplitudes of both the PhNR and cone b wave were reduced at an early stage of diabetic retinopathy. Analysis of the receiver operating characteristic curves demonstrated that the amplitudes and implicit times of the OPs were more sensitive and specific than those of the PhNR in detecting changes of retinal function in the early stages of diabetic retinopathy. CONCLUSIONS: The amplitudes of the OPs and PhNR progressively decrease with the progression of diabetic retinopathy. The PhNR amplitudes were reduced along with the cone b wave, indicating that earlier change of the PhNR in diabetic patients reflects reduced input to the retinal ganglion cell from the distal retina. The amplitudes and implicit times of the OPs are better indicators than those of the PhNR in detecting functional decreases in patients with early diabetic retinopathy.

Action Potentials↗