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Biomedical subjects

Mineo Kondo

Publications and source records attributed to Mineo Kondo.

13 recordsLinked to original sources

Long-term functional synaptic integration of genome-edited retinal organoids in a primate model of macular degeneration.

Retinal organoids represent a promising regenerative strategy for restoring vision in retinal degenerative diseases, but the capacity of host cone bipolar cells in the primate macula to rewire with transplanted photoreceptors has not been established. In this study, we transplanted genome-edited ISL1-/- human retinal organoids lacking ON-bipolar cells into an acute laser-induced macular photoreceptor ablation non-human primate model. Using immunohistochemistry, ultrastructural imaging, and focal macular electroretinography, we demonstrate that host rod and cone bipolar cells actively extend dendrites toward grafted photoreceptors and form synaptic contacts, with evidence of functional signal transmission in a subset of transplanted eyes. Longitudinal, per-eye analyses revealed that host ON-bipolar responses improved in two of four eyes with ISL1-/- graft by up to 21.6% and remained stable for up to 2 years post transplantation. Moreover, OFF-pathway connectivity showed potential progressive maturation, with delayed increase in d-wave after 13 months in one of those eyes. These findings provide the first demonstration of long-term anatomical host-graft synaptic integration in the primate macula, establishing that central cone bipolar circuits retain the capacity for durable rewiring with human stem-cell-derived grafts. Our results highlight ISL1-/- retinal organoids as a promising approach for central vision restoration in macular degeneration.

Animals↗

Foveal thickness in occult macular dystrophy.

PURPOSE: Occult macular dystrophy (OMD) is an inherited macular dystrophy characterized by a progressive macular dysfunction without any visible fundus abnormality. We studied the foveal thickness in patients with OMD using optical coherence tomography (OCT). DESIGN: Observational case series. Foveal thickness by OCT images. METHODS: Foveal thickness obtained from 22 eyes of 11 patients with OMD was compared with that from 27 eyes of 20 age-matched normal controls. RESULTS: Mean foveal thickness in the patients group (96.5 +/- 19.5 microm) was significantly thinner than that in the normal controls (133.3 +/- 9.0 microm, P <.0001, Mann-Whitney U test). Eighteen of 22 eyes with OMD had foveal thickness that were thinner than the lower limit of the normal range. There was no statistically significant correlation between the foveal thickness and visual acuity, age, or duration from onset. CONCLUSION: These results demonstrated that there are significant anatomic changes in the macula of patients with OMD.

Adolescent↗

Macular dystrophy in a Japanese family with fundus albipunctatus.

PURPOSE: To report a Japanese family with fundus albipunctatus and macular dystrophy associated with a mutation in the 11-cis retinol dehydrogenase (RDH5) gene. DESIGN: Observational case report. METHOD: Ophthalmic examinations and DNA analysis were performed. RESULTS: The fundi of a 56-year-old man and his 51-year-old sister showed numerous yellow-white punctata. He also had bull's-eye maculopathy and prepappillary arterial loops, whereas she did not, and his best-corrected visual acuity was impaired, whereas hers was normal. Their kinetic visual fields did, however, show central or paracentral scotoma, and both had tritanomalous color vision. Their scotopic electroretinograms were typical of fundus albipunctatus, and photopic electroretinograms were significantly reduced. A homozygous Gly107Arg mutation in the RDH5 gene was detected in both siblings. CONCLUSIONS: We suggest that the macular dystrophy is caused by the RDH5 gene mutation as a phenotype variation in fundus albipunctatus.

Alcohol Oxidoreductases↗

Optical coherence tomography and focal macular electroretinogram in eyes with epiretinal membrane and macular pseudohole.

PURPOSE: To determine the morphology of macular pseudoholes (MPHs) and the relationship of morphology to macular function. DESIGN: Observational case series. METHODS: Optical coherence tomography (OCT) was performed on 42 eyes of 42 consecutive patients with an epiretinal membrane (ERM) and an MPH. The diameters of the MPH, and the thickness of the foveal and parafoveal retina were measured. Of these 42 eyes, focal macular electroretinograms (FMERGs) were recorded from 22 eyes of 22 patients with a 15 degree stimulus; FMERGs were also recorded with a 5 degree stimulus from 9 eyes of these 22 eyes. RESULTS: In 42 eyes, the mean +/- Standard deviation (SD) diameter (437.7 +/- 172.8 microm) and geometrical shape of the MPHs were not significantly correlated with the visual acuity. The MPHs were divided into 2 types from the OCT images at the base of MPHs; group A had normal thickness (100-199 microm; n = 29), and group B (n = 13) had thicknesses of >or= 200 microm, or thickness < 100 microm, or irregular base. The visual acuity in group A (logarithm of the minimum angle of resolution [log MAR] mean +/- SD:.083 +/-.144) was significantly better than group B (log MAR,.407 +/-.212, P <.0001). There was a significant reduction in the amplitude of all components of FMERGs elicited by the 15 degree stimulus in the affected eyes (mean +/- SE, A-wave: 1.26 +/-.12 microv, B-wave: 3.07 +/-.27 microv, oscillatory potentials: 1.23 +/-.25 microv) compared with the normal fellow eyes (A-wave: 1.58 +/-.13 microv, B-wave: 4.14 +/-.27 microv, oscillatory potentials: 2.35 +/-.29 microv). A significant correlation was found between the relative amplitudes of the B-wave elicited by the 5 degree stimulus and the visual acuity (r =.918, P =.0005). CONCLUSIONS: In eyes with an ERM and an MPH, the visual acuity is generally correlated with the OCT images. Macular function of eyes with an MPH resembles eyes with an ERM without an MPH. The effect of the ERM appears to be different on the base and parafovea of the MPHs.

Adult↗

Functional rescue of N-methyl-N-nitrosourea-induced retinopathy by nicotinamide in Sprague-Dawley rats.

PURPOSE: A single intraperitoneal injection of 60 mg/kg body weight of N-methyl-N-nitrosourea (MNU) into rats results in retinal degeneration over a 7-day period in all treated animals. The purpose of this study was to determine whether nicotinamide (NAM) can lead to a functional rescue of the MNU-induced retinopathy. METHODS: NAM, a water-soluble B-group vitamin (vitamin B( 3)), was administered immediately after MNU injection, and retinas were examined morphologically and functionally. RESULTS: Morphologically, 1000 mg/kg NAM completely suppressed and 50 mg/kg NAM partially suppressed the photoreceptor cell loss. Functionally, scotopic and photopic electroretinographic (ERG) recordings showed that both rod and cone photoreceptor cells were well protected from MNU damage by 1000 mg/kg NAM and partially protected by 50 mg/kg NAM. CONCLUSIONS: NAM can protect photoreceptor cells from MNU-induced retinopathy both structurally and functionally.

Alkylating Agents↗

Function and morphology of macula before and after removal of idiopathic epiretinal membrane.

PURPOSE: To study the function and morphology of the macula of the eye before and after the removal of unilateral idiopathic epiretinal membrane (ERM). METHODS: Focal macular electroretinograms (fmERGs) elicited by a 15 degrees stimulus were recorded in 37 eyes of 37 patients with a unilateral ERM. The amplitudes of the a- and b-waves and the oscillatory potentials (OPs) were compared with the corresponding waves in the normal fellow eyes before and after removal of the ERM. In 29 eyes followed up for more than 6 months after surgery, the fmERGs and foveal and parafoveal thicknesses, measured by optical coherence tomography (OCT), were evaluated. RESULTS: Before surgery, the mean amplitudes of all components of the fmERGs were significantly smaller than in the fellow eyes, with the decrease largest for the OPs, followed by the b-waves and then the a-waves. The eyes with less severely reduced a-wave amplitude (>70% of the fellow eyes) had significantly lower b-wave to a-wave (b/a) ratios. After surgery, the amplitudes of the b-wave and OPs were still significantly smaller in the affected eyes. The mean foveal and parafoveal thicknesses were significantly less after surgery; however, the thickness was still more in the affected eyes. The decrease of the OPs remained after surgery and correlated with increased parafoveal thickness (r = -0.460, P = 0.011). CONCLUSIONS: The decreased fmERGs indicate that macular function is impaired in eyes with ERM. The decrease of the b-wave and OPs in the 29 eyes examined after vitrectomy may be due to the still thickened macular retina.

Aged↗

Multifocal electroretinograms in X-linked retinoschisis.

PURPOSE: To study local retinal cone function in patients with X-linked retinoschisis (XLRS) by multifocal ERGs (mfERGs). METHODS: mfERGs were recorded from seven eyes of seven patients with XLRS (mean age +/- SD, 22.1 +/- 3.2 years; range, 18 to 25 years). Five eyes had microcystic changes in the macula and two eyes had nonspecific macular degeneration. Two eyes had peripheral retinoschisis, and some of the stimuli fell on this area. The stimulus array consisted of 103 hexagons and the total recording time was set at approximately 4 minutes. The amplitudes and implicit times of both focal and summed responses for the first- and second-order kernels were analyzed. RESULTS: The amplitudes of the first-order kernel were markedly reduced in the central retina in all eyes. A large variation was observed in the amplitudes outside the fovea. The amplitudes of the focal cone ERGs at the peripheral retinoschisis did not differ from those recorded from adjacent retinal loci without the retinoschisis. The implicit times of the first-order kernel were significantly delayed, and the amplitudes of the second-order kernels were more affected than the first-order kernels across the whole field in all XLRS eyes. CONCLUSIONS: The cone-mediated retinal responses were more impaired in the central than peripheral retina in eyes with XLRS. Delayed implicit times of the first-order kernel and reduced second-order kernel across the whole testing field in all XLRS eyes suggest that there is widespread cone-system dysfunction in XLRS.

Adolescent↗

Changes in focal macular electroretinograms and foveal thickness after vitrectomy for diabetic macular edema.

PURPOSE: To evaluate the changes in the focal macular electroretinogram (FMERG) and foveal retinal thickness after vitrectomy for diabetic macular edema (DME). METHODS: FMERGs were elicited from 25 eyes of 21 patients (ages 29-75 years) who underwent vitrectomy for DME by a 15 degrees stimulus. A posterior vitreous detachment (PVD) was created during surgery in 19 eyes (group 1), and 4 eyes had a PVD before surgery (group 2). In the remaining 2 eyes, a PVD could not be created (group 3). FMERGs were recorded before and 3, 6, and 12 months after vitrectomy. The foveal thickness, determined by optical coherence tomography (OCT), and visual acuity were measured on the same day as the FMERG recordings. RESULTS: The postoperative visual acuity (logarithm of the minimum angle of resolution [logMAR]) improved gradually after the surgery and was significantly better at 12 months in eyes in group 1 (P = 0.0393). The postoperative mean foveal thickness was significantly less at 3 months after surgery in group 1 eyes (P = 0.0006), and there was a further decrease thereafter. In the 2 eyes in group 3, the decreased foveal thickness 3 and 6 months after surgery became thicker at 12 months. The mean b-wave amplitude of the FMERGs increased significantly at 12 months in group 1 eyes (P = 0.0297). The mean implicit time of a- and b-waves was more delayed at 3 months, and the change in a-wave was statistically significant in group 1 eyes (P = 0.0474). There was a wide range of changes in the b-wave amplitude at 12 months, however, the increase in the b-wave was correlated with the decrease in foveal thickness (r =.49, P = 0.012). CONCLUSIONS: A disparity in the time course and degree of recovery of the foveal thickness and macular retinal function was found in eyes with DME after vitrectomy. Part of the functional recovery could be attributed to decreased retinal thickness and the absorption of the subretinal fluid.

Adult↗

Enhanced S-cone syndrome with subfoveal neovascularization.

PURPOSE: To report a case of enhanced S-cone syndrome associated with subfoveal neovascularization. DESIGN: Observational case report. METHODS: A 23-year-old man, who was first examined at age 9 years, was found to have enhanced S-cone syndrome by clinical, electrophysiological, and molecular genetic examinations. RESULTS: At 9 years of age, a subfoveal neovascularization was present in his right eye and corrected visual acuity was RE: 0.15 and LE: 1.0. After he was 20 years old, cystoid changes in the macula of the left eye appeared and visual acuity, in the left eye, decreased from 1.0 to 0.02. CONCLUSION: The clinical course of enhanced S-cone syndrome is progressive, and we suggest that the subretinal neovascularization is a phenotypic variation of enhanced S-cone syndrome.

Adult↗

Change in full-field ERGs after macular translocation surgery with 360 degrees retinotomy.

PURPOSE: One of the methods used in macular translocation (MT) surgery for subfoveal neovascularization is to create a temporary total retinal detachment followed by a 360 degrees retinotomy. The whole retina is then shifted from the original surface of the retinal pigment epithelium (RPE), resulting in an unusual retina and RPE complex. The purpose of this study was to assess retinal function after MT surgery. METHODS: Full-field electroretinograms (ERGs) were recorded before and 4 to 8 months (mean, 5.4 months) after MT surgery with a 360 degrees retinotomy in 15 consecutive patients with age-related macular degeneration (10 eyes), high myopia (4 eyes), and polypoidal choroidal vasculopathy (1 eye). Their ages ranged from 57 to 74 years. The angle of rotation of the retina ranged from 18 degrees to 45 degrees (mean +/- SE, 30 +/- 2 degrees). In addition to the recording of the standard rod and mixed rod-cone ERGs after 30 minutes of dark adaptation, the cone single flash and 30-Hz flicker ERGs were recorded immediately after a light-adapting background was turned on (LA(0)) and also after 10 minutes of light adaptation (LA(10)). RESULTS: The mean amplitude of the full-field ERGs was reduced after surgery by 44% for the rod response, by 24% for the mixed rod-cone b-wave, by 12% and 35% for the cone single-flash b-wave at LA(0) and 30-Hz flicker ERGs at LA(0), respectively. The mean implicit times were delayed by 8 msec for the rod response, by 2 msec for the mixed rod-cone oscillatory potential (OP1), by 4 msec for the cone single-flash b-wave at LA(0), and by 6 msec for the 30-Hz flicker at LA(0). CONCLUSIONS: These results demonstrated a functional alteration in both the rod and cone components of the ERGs for the entire retina after MT surgery.

Aged↗

Focal macular electroretinograms before and after removal of choroidal neovascular lesions.

PURPOSE: To evaluate the changes in focal macular electroretinograms (fmERGs) after surgical removal of choroidal neovascular (CNV) lesions. METHODS: Fourteen patients (14 eyes) with subfoveal or juxtafoveal CNV associated with age-related macular degeneration and 1 patient with idiopathic CNV underwent vitrectomy and removal of the lesions. fmERGs elicited by a 15 degree stimulus were recorded before and 3 months after surgery. Optical coherence tomography (OCT) was performed to measure the foveal and parafoveal thickness before and 3 months after surgery. RESULTS: Preoperative fmERGs were markedly reduced in all eyes. The mean amplitude of the b-wave in 15 eyes recorded 3 months after surgery increased significantly (P = 0.0022, Wilcoxon signed rank test). In all eyes except two with nearly nonrecordable a- and b- waves, the mean b-wave-to-a-wave ratio after surgery increased significantly in all eyes (P = 0.0330, Wilcoxon signed rank test). The percentage increase in the b-wave amplitude correlated significantly with the percentage decrease in the mean parafoveal retinal thickness (r = 0.688, P = 0.0076). CONCLUSIONS: The decreased macular ERGs were partially recoverable in the early postoperative period. The decreased retinal edema after surgery may have contributed to this recovery.

Adult↗

Post-photoreceptoral activity dominates primate photopic 32-Hz ERG for sine-, square-, and pulsed stimuli.

PURPOSE: To evaluate the relative contributions of photoreceptors and postphotoreceptoral activity to the primate 32-Hz flicker electroretinogram (ERG) elicited by sine-wave, square-wave, and pulse stimuli. METHODS: Flicker 32-Hz ERGs were evoked from four adult rhesus (Macaca mulatta) monkeys using sine-wave, square-wave, and 4-ms pulse trains and xenon photostrobe flicker stimuli. All stimuli had time-averaged luminance of 2.11 log cd/m(2) and were presented on a 1.63-log cd/m(2) white background. Intravitreal injections of DL-2-amino-4-phosphonobutyric acid (APB) and cis-2,3-piperidinedicarboxylic acid (PDA) were given to block activity of ON- and OFF-bipolar cells, respectively. RESULTS: Flicker harmonic analysis showed that the fundamental frequency component provided nearly 75% of the sine-wave and square-wave ERGs versus 63% for 4-ms pulse stimuli and only 49% for strobe flicker. Strobe-flicker responses contained the greatest contribution from higher harmonic components. Removing the ON component with APB increased the fundamental component's amplitudes by more than 30% with sine-wave and square-wave ERGs but had a lesser effect on responses to 4-ms pulses and strobe flicker. When cone responses were isolated by synaptic blockade with APB+PDA, the fundamental component's amplitude was reduced to less than 20% of control for all four stimuli. Postsynaptic ON and OFF components were characterized by amplitude and phase vectors, and sine-wave and square-wave stimuli gave a large phase difference (138 degrees ) between ON and OFF components, which resulted in greater response self-cancellation than with the 4-ms pulse train (121 degrees phase difference) or for strobe flicker (118 degrees ). CONCLUSIONS: The major decrease in flicker responses after photoreceptor synaptic blockade implicates a major contribution from postphotoreceptoral activity to the fundamental flicker component, regardless of the stimulus type. Sine-wave and square-wave stimuli produced larger phase differences between ON- and OFF-pathway components, thereby causing more complete self-cancellation of postphotoreceptoral contributions and revealing slightly greater relative contribution directly from cone photoreceptors with these stimuli than with pulsed stimuli. The direct cone contribution was always small, however, and the clinical point is that 32-Hz flicker ERG amplitudes do not provide an unambiguous assessment of direct cone photoreceptor contribution with any of these stimuli.

Adaptation, Ocular↗