Correction of amblyopia in cats and mice after the critical period.
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ABSTRACT:
SUBMITTER: Fong MF
PROVIDER: S-EPMC8456712 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Preference behaviors are often established during early life, but the underlying neural circuit mechanisms remain unknown. Adapting a unique nesting behavior assay, we confirmed a "critical period" for developing music preference in C57BL/6 mice. Early music exposure between postnatal days 15 and 24 reversed their innate bias for silent shelter, which typically could not be altered in adulthood. Instead, exposing adult mice treated acutely with valproic acid or carrying a targeted deletion of the Nogo receptor (NgR(-/-)) unmasked a strong plasticity of preference consistent with a reopening of the critical period as seen in other systems. Imaging of cFos expression revealed a prominent neuronal activation in response to the exposed music in the prelimbic and infralimbic medial prefrontal cortex only under conditions of open plasticity. Neither behavioral changes nor selective medial prefrontal cortex activation was observed in response to pure tone exposure, indicating a music-specific effect. Open-field center crossings were increased concomitant with shifts in music preference, suggesting a potential anxiolytic effect. Thus, music may offer both a unique window into the emotional state of mice and a potentially efficient assay for molecular "brakes" on critical period plasticity common to sensory and higher order brain areas.
| S-EPMC3477391 | biostudies-other
Project description:PurposeIt has been suggested that amblyopes present impaired motion extrapolation mechanisms. In this study, we used the flash grab effect (FGE), the illusory mislocalization of a briefly flashed stimulus in the direction of a reversing moving background, to investigate whether the amblyopic visual system can correct overextrapolation.MethodsThirteen amblyopes and 13 control subjects participated in the experiment. We measured the monocular FGE magnitude for each subject. Two spatial frequency (2 and 8 cycles), two texture configurations (square wave or sine wave), and two speed conditions (270 degrees/s and 67.5 degrees/s) were tested. In addition, control subjects were further tested in reduced luminance conditions.ResultsCompared with controls, amblyopes exhibited a larger FGE magnitude both in their fellow eye (FE) and amblyopic eye (AE). The FGE magnitude of their AE was significantly larger than that of the FE. In a control experiment, we observed that the FGE magnitude increases with the decreasing of the luminance. The FGE magnitude of amblyopes fall into the same range as that of controls under reduced luminance conditions.ConclusionsWe observed a lager FGE in patients with amblyopia, which indicates that the amblyopic visual system does not accurately correct the overextrapolation when a moving object abruptly reverses its direction. This spatiotemporal processing deficit could be ascribed to delayed visual processing in the amblyopic visual system.
| S-EPMC8711015 | biostudies-literature
Project description:Gama amino butyric acid (GABA) inhibition plays an important role in the onset and offset of the critical period for ocular dominance (OD) plasticity in the primary visual cortex. Previous studies have focused on the involvement of GABAA receptors, while the potential contribution of GABAB receptors to OD plasticity has been neglected. In this study, the GABAB receptor antagonist SCH50911 or agonist baclofen was infused into the primary visual cortex of cats concurrently with a period of monocular deprivation (MD). Using single-unit recordings we found that the OD shift induced by four days of MD during the critical period was impaired by infusion of the antagonist SCH50911, but enhanced by infusion of the agonist baclofen. In contrast, seven days of MD in adult cats did not induce any significant OD shift, even when combined with the infusion of SCH50911 or baclofen. Together, these findings indicate that an endogenous GABAB receptor-mediated inhibition contributes to juvenile, but not adult, OD plasticity.
| S-EPMC5491141 | biostudies-literature
Project description:PurposeTo report data on the response of previously untreated strabismic amblyopia to spectacle correction.DesignProspective, interventional case series.MethodsTwelve patients with previously untreated strabismic amblyopia were prescribed spectacles and examined at five-week intervals until visual acuity was not improved from the prior visit.ResultsAmblyopic eye acuity improved by 2 lines or more from spectacle-corrected baseline acuity in nine of the 12 patients (75%), resolving in three (interocular difference <or=1 line). Mean change from baseline to maximum improvement was 2.2 +/- 1.8 lines. Improvement continued for up to 25 weeks.ConclusionsThese results support the suggestion from a prior study that strabismic amblyopia can improve and even resolve with spectacle correction alone. Larger studies with concurrent controls are needed to confirm or refute these findings.
| S-EPMC2041929 | biostudies-literature
Project description:IntroductionAmblyopia therapy appears to be most effective in children under the age of 7 years, but results from randomized control trials (RCTs) have shown that occlusion therapy and/or atropine penalization therapy may improve visual acuity in an older age group. Which of these two therapies is the most effective with fewer adverse effects in an older age group has not yet been agreed upon.MethodsWe systematically searched the literature for RCTs that compared atropine penalization therapy and occlusion therapy in terms of their visual acuity outcomes and adverse events and performed a meta-analysis on the visual acuity data obtained. The adverse effects reported and their implications for clinical practice are discussed.ResultsTwo RCTs were identified, with the authors of both concluding that there was no detectable difference between the two therapies for the age groups they studied. The mean difference between atropine penalization and occlusion therapies was calculated to be - 0.01 logMAR (95% confidence interval - 0.07 to 0.03 logMAR) in favor of occlusion therapy, and no statistical difference between the two groups was detected (P = 0.45). Neither study detected a marked difference in terms of reported adverse effects from the two interventions.ConclusionBased on the results of our meta-analysis we conclude that there is no difference in visual acuity outcomes between atropine penalization therapy and occlusion therapy after 17 to 24 weeks of treatment in children aged 7-12 years. Further evidence to determine the efficacy of amblyopia therapy for an older patient population is required before studies comparing atropine penalization and occlusion therapy in patients older than 12 years can be performed. Atropine penalization therapy may cause more frequent minor adverse effects, such as light sensitivity, but in the clinical setting this needs to be balanced with the potential practical benefits of twice-weekly eye drops versus daily occlusion.FundingThe funding for this study was provided by the National Institute for Health Research (NIHR) and Health Education England (HEE). A plain language summary is available for this article.
| S-EPMC6258585 | biostudies-literature
Project description:In contrast to the prenatal development of the cerebral cortex, when cell production, migration, and layer formation dominate, development after birth involves more subtle processes, such as activity-dependent plasticity that includes refinement of synaptic connectivity by its stabilization and elimination. In the present study, we use RNA-seq with high spatial resolution to examine differential gene expression across layers 2/3, 4, 5, and 6 of the mouse visual cortex before the onset of the critical period of plasticity [postnatal day 5 (P5)], at its peak (P26), and at the mature stage (P180) and compare it with the prefrontal association area. We find that, although genes involved in early developmental events such as cell division, neuronal migration, and axon guidance are still prominent at P5, their expression largely terminates by P26, when synaptic plasticity and associated signaling pathways become enriched. Unexpectedly, the gene expression profile was similar in both areas at this age, suggesting that activity-dependent plasticity between visual and association cortices are subject to the same genetic constraints. Although gene expression changes follow similar paths until P26, we have identified 30 regionally enriched genes that are prominent during the critical period. At P180, we identified several hundred differentially expressed gene isoforms despite subsiding levels of gene expression differences. This result indicates that, once genetic developmental programs cease, the remaining morphogenetic processes may depend on posttranslational events.
| S-EPMC4491803 | biostudies-other
Project description:Dichoptic movie viewing has been shown to significantly improve visual acuity in amblyopia in children. Moreover, short-term occlusion of the amblyopic eye can transiently increase its contribution to binocular fusion in adults. In this study, we first asked whether dichoptic movie viewing could improve the visual function of amblyopic subjects beyond the critical period. Secondly, we tested if this effect could be enhanced by short-term monocular occlusion of the amblyopic eye. 17 subjects presenting stable functional amblyopia participated in this study. 10 subjects followed 6 sessions of 1.5 hour of dichoptic movie viewing (nonpatched group), and 7 subjects, prior to each of these sessions, had to wear an occluding patch over the amblyopic eye for two hours (patched group). Best-corrected visual acuity, monocular contrast sensitivity, interocular balance, and stereoacuity were measured before and after the training. For the nonpatched group, mean amblyopic eye visual acuity significantly improved from 0.54 to 0.46 logMAR (p < 0.05). For the patched group, mean amblyopic eye visual acuity significantly improved from 0.62 to 0.43 logMAR (p < 0.05). Stereoacuity improved significantly when the data of both groups were combined. No significant improvement was observed for the other visual functions tested. Our training procedure combines modern video technologies and recent fundamental findings in human plasticity: (i) long-term plasticity induced by dichoptic movie viewing and (ii) short-term adaptation induced by temporary monocular occlusion. This passive dichoptic movie training approach is shown to significantly improve visual acuity of subjects beyond the critical period. The addition of a short-term monocular occlusion to the dichoptic training shows promising trends but was not significant for the sample size used here. The passive movie approach combined with interocular contrast balancing even over such a short period as 2 weeks has potential as a clinical therapy to treat amblyopia in older children and adults.
| S-EPMC6735187 | biostudies-literature
Project description:The aim of this study was to assess the effect of wearing optical correction on the choroidal structure in eyes of children with anisohypermetropic amblyopia. This study was conducted at the Nara Medical University Hospital and at the Tokushima University Hospital. Twenty-nine anisohypermetropic amblyopic eyes and their fellow eyes of 29 amblyopic patients (mean age, 5.7 ± 1.7 years, range 3- to 8-years) and twenty eyes of 20 age-similar control children (4.9 ± 0.8 years, range 4- to 6-years) were studied. All patients wore optical correction and 15 patients had both optical correction and patching. The values at the baseline were compared to that at one year later. The binarization method was used to determine the total, luminal, and stromal areas of the choroid in the enhanced depth imaging optical coherence tomographic images. The best-corrected visual acuity (BCVA) of the amblyopic eyes was significantly improved after the one-year period. A large luminal area was characteristic of the amblyopic eye at the baseline, and it was significantly reduced after the optical treatment. The stromal area widened significantly in the amblyopic and fellow eyes after one year whereas there were no significant changes in the choroid of the control eyes after one year. After one-year of optical correction, the luminal/stromal ratios in the amblyopic and fellow eyes were decreased and were then not significantly different from that of the normal control eyes. There was a significant and positive correlation between the improvement of the BCVA and the stromal area at the baseline (r = 0.64, P = 0.001). Wearing corrective lenses on the amblyopic eyes improves the BCVA, and the choroidal structure of the amblyopic eye becomes closer to that of the control eyes. The narrowed luminal area is a specific response of the amblyopic eye associated with the correction of the refractive error. The larger stromal area in the amblyopic eyes at the baseline is a predictive factor for improvements of the BCVA.
| S-EPMC7179822 | biostudies-literature
Project description:Perceptual learning is considered a potential treatment for amblyopia even in adult patients who have progressed beyond the critical period of visual development because adult amblyopes retain sufficient visual plasticity. When perceptual learning is performed with the correction of high-order aberrations (HOAs), a greater degree of neural plasticity is present in normal adults and those with highly aberrated keratoconic eyes. Because amblyopic eyes show more severe HOAs than normal eyes, it is interesting to study the effects of HOA-corrected visual perceptual learning in amblyopia. In the present study, we trained twenty-six older child and adult anisometropic amblyopes while their HOAs were corrected using a real-time closed-loop adaptive optics perceptual learning system (AOPL). We found that adaptive optics (AO) correction improved the modulation transfer functions (MTFs) and contrast sensitivity functions (CSFs) of older children and adults with anisometropic amblyopia. When perceptual learning was performed with AO correction of the ocular HOAs, the improvements in visual function were not only demonstrated in the condition with AO correction but were also maintained in the condition without AO correction. Additionally, the learning effect with AO correction was transferred to the untrained visual acuity and fellow eyes in the condition without AO correction.
| S-EPMC5067678 | biostudies-literature
Project description:Alterations in sensory processing constitute prominent symptoms of fragile X syndrome; however, little is known about how disrupted synaptic and circuit development in sensory cortex contributes to these deficits. To investigate how the loss of fragile X mental retardation protein (FMRP) impacts the development of cortical synapses, we examined excitatory thalamocortical synapses in somatosensory cortex during the perinatal critical period in Fmr1 knockout mice. FMRP ablation resulted in dysregulation of glutamatergic signaling maturation. The fraction of silent synapses persisting to later developmental times was increased; there was a temporal delay in the window for synaptic plasticity, while other forms of developmental plasticity were not altered in Fmr1 knockout mice. Our results indicate that FMRP is required for the normal developmental progression of synaptic maturation, and loss of this important RNA binding protein impacts the timing of the critical period for layer IV synaptic plasticity.
| S-EPMC2825250 | biostudies-literature