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Mineo Kondo

Publications and source records attributed to Mineo Kondo.

At least 19 recordsLinked to original sources
PubMed2026

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↗
PubMed2006

Effect of axial length on laser spot size during photodynamic therapy: an experimental study in monkeys.

PURPOSE: To investigate the effect of shorter axial length on the laser spot size and laser energy during photodynamic therapy (PDT) in monkeys. DESIGN: Experimental study with four rhesus monkeys. METHODS: PDT was performed on the normal retina of monkeys whose ocular axial lengths are shorter (19.55 to 20.25 mm) than that of humans. After the PDT, the eyes were enucleated, and the diameter of the irradiated laser spot was measured with a microcaliper. RESULTS: The area of actual laser spot was only 0.56 to 0.61 times of the planned area, which indicated that the laser energy/area was 1.64 to 1.78 times more intense than planned initially. CONCLUSION: These results are the in vivo demonstration that the diameter of PDT laser spot is smaller for eyes with shorter axial lengths.

Animals↗
PubMed2006

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↗
PubMed2006

Selective amplitude reduction of the PhNR after macular hole surgery: ganglion cell damage related to ICG-assisted ILM peeling and gas tamponade.

PURPOSE: The photopic negative response (PhNR) is a negative component of the photopic electroretinogram (ERG) that is observed after the b-wave and is thought to originate mainly from the activity of ganglion cells and their axons. The purpose of this study was to determine whether there are subclinical functional changes in the inner retina after macular hole surgery, by recording the PhNR before and after surgery. METHODS: In addition to the routine ophthalmic examinations, photopic ERGs were recorded in 16 eyes with an idiopathic macular hole, before and 3 months after surgery. Photopic ERGs were elicited by white Ganzfeld flashes on a rod-suppressing blue background. The amplitude of the PhNR and the a- and b-waves of the photopic ERGs before and after surgery were compared. PhNRs were also recorded in 14 eyes with epiretinal membrane, before and after surgery. RESULTS: Macular holes were closed and visual acuities were improved without any serious complications in all eyes with a macular hole. The amplitude of the PhNR was significantly reduced after surgery (P < 0.05), whereas the amplitude of the photopic a- and b-waves were not significantly altered. For eyes with an epiretinal membrane, the mean amplitude of the PhNR was slightly decreased after the surgery, but the degree of reduction was only one half of that after macular hole surgery. CONCLUSIONS: These results suggest that there are some functional impairments in the inner retina after macular hole surgery, even though the patients did not show any reduction on subjective visual tests. The PhNR can be a useful clinical test to assess the inner retinal function objectively, before and after vitreoretinal surgery.

Adaptation, Ocular↗
PubMed2005

Contribution of retinal neurons to d-wave of primate photopic electroretinograms.

The purpose of this study was to determine the contribution of different types of retinal neurons to the d-wave of the primate electroretinogram using pharmacological agents. NMDA + TTX was used to suppress inner retinal activity, and APB and PDA to block the activity of the ON- and OFF-pathways, respectively. Results indicated that the inner retinal neurons had a small but certain contribution to the d-wave. The initial rapid phase of the d-wave originates from the activity of the cone OFF-pathway nearly exclusively, and the later slow phase is shaped by the cone photoreceptors. The cone ON-pathway acts in a direction opposite to that of the other components.

Aminobutyrates↗
PubMed2005

Physiological function of S-cone system is not enhanced in rd7 mice.

The rd7mouse is a mutant mouse with a relatively late development of retinal degeneration. Earlier studies have shown that rd7 mice have a distinctive pattern of retinal dysplasia with an increased number of cone cells, particularly those with S (short wavelength)-opsin immunoreactivity. These alterations of the rd7 retina are caused by a mutation in the photoreceptor cell-specific nuclear receptor gene, Nr2e3, which is involved in the signaling pathway regulating photoreceptor cell differentiation, cell maintenance, and cell-cell interactions. The purpose of this study was to determine the physiological properties of the rd7 retina using electroretinographic (ERG) techniques. We found that the maximal a-wave amplitude of the ERG in rd7 mice was already reduced to half of the congenic controls at 6 weeks of age with normal phototransduction sensitivity. The photopic ERGs of rd7 mice were not supernormal, and the amplitudes of the S-cone ERGs were not significantly different from those recorded in controls. These results suggested that even though the number of cones expressing S-opsin is increased, the physiological function of the S-cone system is not enhanced in rd7 mice.

Animals↗
PubMed2005

Retinal G-substrate, potential downstream component of NO/cGMP/PKG pathway, is located in subtype of retinal ganglion cells and amacrine cells with protein phosphatases.

The aim of this study was to determine the distribution and function of G-substrate, a specific substrate of the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP)-cGMP-dependent protein kinase (PKG) signaling pathway, in normal rat retina and in G-substrate knockout mice. The retinas of adult wild-type rats and mice and G-substrate knockout mice were studied immunohistologically to characterize the upstream and downstream components of the NO-cGMP-PKG pathway. Immunoblot analysis showed that the molecular weight of retinal G-substrate was similar to that of cerebellar G-substrate. In adult rats and mice, retinal G-substrate was located in a subpopulation of amacrine cells and in C38-positive retinal ganglion cells (RGCs) but not in alpha RGCs. In addition, retinal G-substrate was co-expressed with other upstream and downstream signaling components of the NO-cGMP-PKG-G-substrate-phosphatase pathway in the adult retina. Electroretinographic (ERG) analysis demonstrated that there was no significant difference between the ERGs of wild-type and G-substrate knockout mice. These results suggest that retinal G-substrate plays a role as a downstream component of the NO-cGMP-PKG pathway. The co-localization of retinal G-substrate with protein Ser/Thr phosphatases suggests that it acts as an endogenous protein phosphatase inhibitor as in the cerebellum.

Amacrine Cells↗
PubMed2005

Dissociated optic nerve fiber layer appearance after internal limiting membrane peeling for idiopathic macular holes.

PURPOSE: To investigate the characteristics and incidence of a dissociated optic nerve fiber layer (DONFL) appearance in eyes after idiopathic macular hole surgery. DESIGN: Retrospective, nonrandomized, comparative interventional case series. PARTICIPANTS: Ninety-one eyes with idiopathic macular holes that were closed after 1 pars plana vitrectomy were studied. Among these, 67 eyes had the internal limiting membrane (ILM) peeled (ILM-peeled), and 24 did not have the ILM peeled (ILM-unpeeled). METHODS: All patients received a complete ophthalmologic examination and color fundus photography preoperatively and postoperatively. Twenty ILM-peeled eyes and 9 ILM-unpeeled eyes were also examined by optical coherence tomography (OCT3), microperimetry by scanning laser ophthalmoscope (SLO), and macular sensitivity measurements by Humphrey visual field testing more than 4 months after the vitrectomy. MAIN OUTCOME MEASURES: Development of a DONFL on fundus photographs and OCT3, and the functional evaluation of a DONFL by best-corrected visual acuity, SLO-microperimetry, and Humphrey visual field testing. RESULTS: In 67 ILM-peeled eyes, a DONFL appearance was found in 36 eyes (54%) in color fundus photographs. A DONFL appearance was not detected in any of the 24 ILM-unpeeled eyes. Focal dehiscence of the optic nerve fiber layer was found in all 20 examined eyes by OCT3. No scotoma was found corresponding to the DONFL by SLO microperimetry. The best-corrected visual acuity and macular sensitivity were not significantly different in eyes with and without a DONFL appearance (P>0.05). A DONFL appearance was not detected in all 20 eyes examined within 1 month after surgery, was detected in all 16 eyes examined between 1 and 3 months, and no new cases were detected after 3 months. The DONFL appearance became more distinct until about 6 months after first detection and seemed not to change subsequently. CONCLUSIONS: The DONFL appearance in about half of the eyes with ILM peeling and none in eyes without ILM peeling strongly suggest that the DONFL appearance is related to ILM peeling. The OCT findings in eyes with no functional abnormality by SLO microperimetry suggested that the DONFL is due to a dehiscence of the optic nerve fiber layer and not a true nerve fiber layer defect.

Aged↗
PubMed2005

Abnormalities caused by carbohydrate alterations in Ibeta6-N-acetylglucosaminyltransferase-deficient mice.

Ibeta6-N-acetylglucosaminyltransferase (IGnT) catalyzes the branching of poly-N-acetyllactosamine carbohydrate chains. In both humans and mice, three spliced forms of IGnT have been identified, and a common exon is present in all of them. We generated mice deficient in the common exon to understand the physiological function of poly-N-acetyllactosamine branching. IGnT activity was abolished in the stomach, kidney, bone marrow, and cerebellum of the deficient mice, while a low level of the activity persisted in the small intestine. Immunohistochemical analysis confirmed the loss of I antigen from the lung, stomach, and kidney. The deficient mice had reduced spontaneous locomotive activity. The number of peripheral blood lymphocytes was also reduced and renal function decreased in the deficient mice. Furthermore, in aged mice, vacuolization occurred in the kidney, and epidermoid cysts were frequently formed. However, cataracts did not develop earlier in the deficient mice. Decreased levels of lysosomal proteins, LAMP-2 and synaptotagmin VII, were found in the kidney of the deficient mice and correlated with renal abnormalities.

Animals↗
PubMed2005

Cone and rod dysfunction in fundus albipunctatus with RDH5 mutation: an electrophysiological study.

PURPOSE: A prior study showed that some patients with fundus albipunctatus (FA) have severely reduced full-field cone ERGs. The purpose of this study was to investigate the frequency of cone dysfunction and to determine the cause of the reduced full-field cone ERGs in patients with FA and whether the rod system is affected in patients with FA. METHODS: Sixteen consecutive patients with FA (from 1993 to 2003; eight males, eight females; mean age, 25.4 years) with an RDH5 gene mutation were studied. The amplitudes and implicit times of the standard cone ERGs in the patients with FA were compared to those obtained from normal subjects (n = 55). The a-waves of cone ERGs were also elicited by a bright flash and were fitted to a mathematical model of the a-wave. Rod ERG responses were elicited by dim blue flashes after 3 hours of dark adaptation. RESULTS: The amplitude of the b-wave of the cone ERG in the FA group varied considerably from within the normal limits to markedly decreased. Six of 16 patients with FA had b-wave amplitudes that were smaller than the lowest limit of the control subjects. The degree of cone dysfunction tended to be more severe in older patients. The analysis of the cone a-wave demonstrated that R(m) (maximal response amplitude) in the patients with FA with reduced standard cone ERGs was significantly smaller than that in control subjects. Rod ERGs were also reduced in the patients with FA who had reduced cone ERGs. CONCLUSIONS: In patients with FA, 38% had extensive cone dysfunction. The reduced full-field cone ERGs were mainly due to the loss of cone photoreceptors, and the rod system was also affected in some patients.

Adolescent↗
PubMed2005

Bagolini striated glasses test and lesions of the optic chiasm.

PURPOSE: To examine the usefulness of the Bagolini Striated Glasses Test to identify patients with a lesion of the optic chiasm. SUBJECTS AND METHODS: Twelve patients who were diagnosed with a lesion of the optic chiasm by MRI were examined with the Bagolini Striated Glasses Test. Discrepancies of the test between monocular and binocular conditions were analyzed. Visual acuity, visual field and stereo tests were also administered and assessed. RESULTS: Nine out of 12 cases (75%) showed conflicting results with the Bagolini Striated Glasses Test between monocular and binocular conditions. With monocular testing, essentially normal stripes were observed in each eye. In binocular testing, stripes which were projected upon nasal retina were suppressed bilaterally (bitemporal hemianopia pattern) ("mountain pattern") or monocularly (monocular temporal hemianopia pattern). CONCLUSION: The Bagolini Striated Glasses Test can be used as a simple differential diagnostic test for lesions of the optic chiasm. The "mountain pattern" seen binocularly on this test may be pathognomonic for such lesions, which may otherwise be asymptomatic and/or overlooked.

Adenoma↗
PubMed2004

Changes in foveal thickness and macular function after transpupillary thermotherapy for age-related macular degeneration.

PURPOSE: To evaluate the effect of transpupillary thermotherapy (TTT) on foveal thickness and macular function in eyes with choroidal neovascularization (CNV) associated with age-related macular degeneration. METHODS: Sixteen eyes with occult CNV and 6 eyes with classic CNV were treated with TTT. Optical coherence tomography and focal macular electroretinograms (FMERGs) elicited by a 15-degree stimulus were performed before, 3 months after TTT in 22 eyes and 6 months after TTT in 18 eyes. RESULTS: Before TTT, the fovea in 20 of the 22 eyes with CNV was significantly thicker than that of normal subjects. The foveal thickness was reduced after TTT in 11 of 14 eyes with occult CNV and remained unchanged in 2 eyes. One eye with occult CNV before TTT developed a classic CNV with significant macular edema and increased foveal thickness 3 months after TTT. The amplitudes of the FMERGs were reduced in all eyes before TTT. In eyes with occult CNV, the mean b-wave amplitude increased significantly after TTT (p = 0.0260 at 3 months, p = 0.0142 at 6 months). When the change of foveal thickness was less than 20% after TTT, all eyes with occult CNV had a 30% or more increase in the b-wave amplitude. In eyes with classic CNV, the mean amplitude of the a- and b-waves did not change significantly after TTT. CONCLUSIONS: TTT improves macular function in eyes with occult CNV associated with age-related macular degeneration more when the change of foveal thickness is slight.

Aged↗
PubMed2004

Effects of flanking genes on the phenotypes of mice deficient in basigin/CD147.

The induction of null mutations by means of homologous recombination is a powerful technique for clarifying the biological activities of target genes. However, the problems of the genetic background and flanking genes should be borne in mind. Here we employed a breeding strategy to compare three lines of mice deficient in the basigin (Bsg)/CD147 gene. The first line was F2 from F1 hybrid offspring of the 129/SV chimera and C57BL/6J. The second one was from a C57BL/6J congenic line. Both lines showed high embryonic lethality, sterility, and blindness. The third one was 'reverse F2' from 'reverse F1' hybrid offspring of the C57BL/6J congenic line and 129/SV. Surprisingly, this line showed a normal birth rate, while sterility and blindness persisted. Our results clearly separate the effects of the induced null mutation from those of flanking genes and the genetic background, and provide a useful means of investigating the biological functions of Bsg.

Animals↗
PubMed2004

Primate Retinal Signaling Pathways: Suppressing ON-Pathway Activity in Monkey With Glutamate Analogues Mimics Human CSNB1-NYX Genetic Night Blindness.

Retinal on-pathway dysfunction is implicated in human complete-type congenital stationary night blindness (CSNB1), a Mendelian genetic condition that results from mutations in the NYX gene encoding the protein nyctalopin. We probed cone pathway dysfunction in four human genotyped CSNB1 affected males by electroretinogram (ERG) recordings elicited with photopic sinusoidal and rapid-on/off-ramp flicker stimuli that are reputed to elicit on/off-pathway activity selectively. Results were analyzed in relation to ERG abnormalities created in anesthetized non-human primates by intravitreal application of glutamate analogues that selectively suppress retinal on- or off-pathway bipolar cell activity. 2-amino-4-phosphonobutyric acid (APB), which selectively blocks light responses of on-pathway depolarizing bipolar cells, fully recreated the essential ERG abnormalities found for human CSNB1 under the condition that the off-pathway remained active. Both CSNB1-NYX humans and APB-treated monkey retina lacked the normal amplitude dip and the phase deflection that occurs in the fundamental component near 12 Hz for sinusoidal flicker stimuli. The off-pathway suppressing agent, cis-2,3-piperidine-dicarboxylic acid (PDA), gave results in monkey quite discordant to CSNB1 human for sinusoidal stimulation. The results implicated a specific on-pathway signaling deficiency in CSNB1-NYX males with no evidence of off-pathway involvement. Likewise, rapid-on/off ramping stimuli also indicated that the functional deficit was localized to the on pathway. Analysis of non-human primate retinal responses after drug application demonstrated a complexity to on/off-pathway contributions to ramping on/off ERG responses not previously anticipated. These results support the hypothesis that nyctalopin acts principally or exclusively within the on pathway at the level of depolarizing bipolar cells, and thus human CSNB1-NYX subjects provide an opportunity to probe the primate visual system for consequences of on-pathway deficits.

Adolescent↗
PubMed2004

Peripheral cone dystrophy: a variant of cone dystrophy with predominant dysfunction in the peripheral cone system.

PURPOSE: To determine the phenotype of 3 patients from 2 pedigrees with an unusual form of cone dystrophy in which the peripheral cone system is more affected than the central cone system, and whose rod system is relatively normal. DESIGN: Three observational case reports with electrophysiologic and psychophysical studies. METHODS: Three patients underwent fundus photography, fluorescein angiography, color vision testing, Goldmann visual field testing, full-field electroretinograms (ERGs), focal macular cone ERGs, and rod-cone perimetry, in addition to routine ophthalmologic examinations. Multifocal ERGs also were recorded from 2 patients. RESULTS: The fundus examination and fluorescein angiogram results essentially were normal except for a mild temporal pallor of the optic disc in 2 patients. The corrected visual acuity ranged from 20/16 to 20/100. Color vision was normal in 1 patient, but was abnormal in 2 patients. A relative paracentral scotoma was detected in 2 patients. Full-field ERG cone responses were reduced significantly, but rod responses were normal in all patients, as in patients with typical cone dystrophy. However, the focal macular cone ERGs were well preserved in all patients. Psychophysical rod-cone perimetry demonstrated that the peripheral cone system was impaired, whereas the rod sensitivity was completely normal. The results of the multifocal ERG in 2 patients supported the findings made by the full-field and focal macular ERGs. CONCLUSIONS: These findings demonstrate that there is a subgroup of patients with cone dystrophy where the peripheral cone system is more affected than the central cone system.

Adult↗
PubMed2004

Changes in focal macular ERGs after macular translocation surgery with 360 degrees retinotomy.

PURPOSE: To evaluate the short- and long-term changes of focal macular electroretinograms (fmERGs) after macular translocation with 360 degrees retinotomy. METHODS: This was a retrospective study. fmERGs were recorded in 19 eyes of 19 consecutive patients who underwent macular translocation with 360 degrees retinotomy for choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD; 17 eyes) or polypoidal choroidal vasculopathy (2 eyes). The changes in the fmERGs, recorded before, shortly after (6-12 months; mean 8.3 months), and more than 18 months (18-30 months; mean 22.4 months) after surgery from 12 eyes, were analyzed. A 15 degrees stimulus centered on the fovea was used to elicit the fmERGs. RESULTS: The mean logarithm of minimum angle of resolution (logMAR) was 1.06 +/- 0.07 (20/230) before surgery, 0.78 +/- 0.08 (20/121) early after surgery (n = 19), and 0.64 +/- 0.07 (20/87) late after surgery (n = 12). These improvements in visual acuity were significant (P = 0.0074, P = 0.0050, respectively). Before surgery, the amplitudes of all components of the fmERGs were markedly reduced in all eyes. The mean b-wave amplitude in 17 AMD eyes recorded early after surgery was significantly larger (P = 0.0262), and the mean a-wave amplitude was also increased but not significantly (P = 0.1180). The mean amplitudes of the a- and b-waves in 10 AMD eyes recorded after 18 months were significantly larger than those before the surgery (P = 0.0218, and P = 0.0284). The mean implicit time of the b-wave in 17 AMD eyes decreased early after surgery, and a further decrease was detected at the later testing time. CONCLUSIONS: These results indicate that macular function is partially recoverable after macular translocation in some patients.

Aged↗
PubMed2004

Luminance dependence of neural components that underlies the primate photopic electroretinogram.

PURPOSE: At lower stimulus intensities, the amplitude of the photopic flash ERG b-wave increases with increasing stimulus intensities, but then plateaus and decreases at higher stimulus intensities (the "photopic hill"). The purpose of this study was to determine the mechanism underlying this unusual phenomenon. METHODS: Five adult monkeys (Macaca mulatta and M. fascicularis) were studied. Stimuli were obtained from xenon strobe flashes, and the intensity was reduced by neutral-density filters in 0.4-log unit steps. N-methyl-D-aspartic acid and tetrodotoxin citrate (NMDA+TTX) were used to suppress inner retinal activities and L-2 amino-4-phosphonobutyric acid (APB) and cis-2,3 piperidine dicarboxylic acid (PDA) to block postreceptoral ON- and OFF-pathway activities. The postsynaptic ON- and OFF-components were isolated by subtracting the postdrug ERGs from the predrug ERGs. RESULTS: The intensity-response curve of the photopic b-wave obtained after the intravitreal injection of TTX+NMDA had the same shape as a photopic hill, suggesting that the contribution from the inner retinal neurons to the photopic hill is not significant. At low and intermediate intensities, the photopic b-wave was mainly shaped by the overlapping of two positive peaks from the ON- and OFF-components. However, the amplitude of the positive peak from the ON-component became smaller and broader at higher stimulus intensities. In addition, the timing of the positive peak of the OFF-component was gradually delayed with increasing intensities. After APB+PDA, the remaining cone photoreceptor component contributed only to the negative a-wave at all stimulus intensities. CONCLUSIONS: The photopic hill in the primate ERG results mainly from two factors: the reduction of the ON-component amplitude at higher intensities and the delay in the positive peak of the OFF-component at higher intensities.

Adult↗