Activation of p38 MAPK hinders the reactivation of visual cortical plasticity in adult amblyopic mice.

OBJECTIVE: To investigate the impact of p38 mitogen-activated protein kinase (MAPK) signaling on reactivating visual cortical plasticity in adult amblyopic mice. MATERIALS AND METHODS: Reverse suture (RS), environment enrichment (EE), and combined with left intracerebroventricular injection of p38 MAPK inhibitor (SB203580, SB) or p38 MAPK agonist (dehydrocorydaline hydrochloride, DHC) were utilized to treat adult amblyopic mice with monocular deprivation (MD). The visual water task, visual cliff test, and Flash visual-evoked potential were used to measure the visual function. Then, Golgi staining and transmission electron microscopy were used to assess the reactivation of structural plasticity in adult amblyopic mice. Western blot and immunohistochemistry detected the expression of ATF2, PSD-95, p38 MAPK, and phospho-p38 MAPK in the left visual cortex. RESULTS: No statistically significant difference was observed in the visual function in each pre-intervention group. Compared to pre-intervention, the visual acuity of deprived eyes was improved significantly, the impairment of visual depth perception was alleviated, and the P wave amplitude and C/I ratio were increased in the EE + RS, the EE + RS + SB, and the EE + RS + DMSO groups, but no significant difference was detected in the EE + RS + DHC group. Compared to EE + RS + DHC group, the density of dendritic spines was significantly higher, the synaptic density of the left visual cortex increased significantly, the length of the active synaptic zone increased, and the thickness of post-synaptic density (PSD) thickened in the left visual cortex of EE + RS, EE + RS + SB, and EE + RS + DMSO groups. And that, the protein expression of p-p38 MAPK increased while that of PSD-95 and ATF2 decreased significantly in the left visual cortex of the EE + RS + DHC group mice. CONCLUSION: RS and EE intervention improved the visual function and synaptic plasticity of the visual cortex in adult amblyopic mice. However, activating p38 MAPK hinders the recovery of visual function by upregulating the phosphorylation of p38 MAPK and decreasing the ATF2 protein expression.

Regulatory role of the p38 MAPK/ATF2 signaling pathway in visual function and visual cortical plasticity in mice with monocular deprivation.

BACKGROUND: This study aimed to examine the role of the p38 mitogen-activated protein kinase (MAPK)/ activating transcription factor 2 (ATF2) signaling in visual function impairment and visual cortical plasticity in mice with monocular deprivation (MD). METHODS: Visual behavioral tests, including visual water task, visual cliff test, and flash visual evoked potential, were performed on each group. We studied the density of dendritic spines and the synaptic ultrastructure by Golgi staining and transmission electron microscope. We performed Western blot and immunohistochemistry and detected the expression of ATF2, PSD-95, p38 MAPK, and phosphor-p38 MAPK in the left visual cortex. RESULTS: In the MD + SB group, the visual acuity in deprived eyes substantially improved, the impairment of visual depth perception was alleviated, and the P wave amplitude and C/I ratio increased. The density of dendritic spines and the numerical density of synapses increased significantly, the width of the synaptic cleft decreased significantly, and the length of the active synaptic zone and the thickness of post-synaptic density (PSD) increased substantially. The protein expression of phosphor-p38 MAPK decreased, whereas that of PSD-95 and ATF2 increased significantly. CONCLUSIONS: Inhibiting the phosphorylation of p38 MAPK and negative feedback upregulated ATF2 expression, alleviated damage to visual function, and protected against synaptic plasticity in mice with MD.

The long-term surgical outcomes of lateral rectus advancement in consecutive esotropia.

PURPOSE: To evaluate the long-term surgical efficacy of lateral rectus advancement (LRadv) in patients with consecutive esotropia (CET). METHODS: The medical records of 30 patients who developed CET after bilateral lateral rectus (BLR) recession for exotropia (XT) between 2012 and 2020 were reviewed. The characteristics of patients during their XT surgery were summarized. Among them, 15 patients who underwent LRadv as CET treatment with at least a 1-year follow-up were included to evaluate the long-term efficacy of this surgical approach. The main outcomes were the pre- and post-operative angle of deviation after LRadv. Surgical success was defined as the postoperative deviation within 10 prism diopters (PD), and reoperation was not needed. All data were expressed as median and interquartile ranges. RESULTS: The median follow-up was 34 months after LRadv surgery. The median postoperative deviation ranged from 28 to 1 PD at 1 year (P < 0.05) and to 5 PD at the final follow-up (P < 0.05). The deviation at each follow-up time showed no statistically significant difference (P > 0.05). The final surgical success was reduced compared to 1 day and 1 year postoperatively (60% VS 100% and 66.7%, respectively). Undercorrection and overcorrection both occurred at the final follow-up. CONCLUSION: Although the immediate surgical outcome of LRadv was satisfactory, the success rate reduced with time, which suggests long-term observation is necessary to detect and timely provide appropriate interventions for overcorrection or undercorrection.

Clinical efficacy of the partial rectus muscle transportation procedure for paralytic strabismus.

AIM: To analyze the clinical efficacy of the partial rectus muscle transportation (PRT) procedure for paralytic strabismus due to single rectus muscle palsy. METHODS: In total, 28 patients (31 eyes) who underwent the PRT procedure for paralytic strabismus due to single rectus muscle palsy were retrospectively examined. The following data were collected pre- and postoperatively: angle of deviation in the primary position, presence of diplopia in the primary position, presence of compensatory head posture, and motility of the affected eye. The follow-up period was 6mo. RESULTS: Based on the preoperative and intraoperative findings, different operations were performed: 2 eyes were treated with PRT, 26 eyes were treated with PRT combined with the recession of the antagonist muscle (Am) of the paralytic rectus muscle, and 3 eyes were treated with PRT along with the recession of the Am and the yoke muscle (Ym). On the first day after the operation, 24 patients were found to be orthophoric in the primary position, without diplopia or abnormal head posture. Moreover, 2 patients with monocular lateral rectus muscle palsy had mild overcorrection to 5 prism diopters (PD) and 8 PD, respectively, whereas 2 patients with binocular lateral rectus muscle palsy had mild undercorrection to 8 PD and 10 PD, respectively. During the 6-month follow-up period, the mean deviation was rectified from 96.79±41.21 PD to 0.64±2.38 PD (t=12.48, P<0.001), whereas the deviations in the 2 patients with mild overcorrection were corrected to orthotropia. The mean preoperative limitation of motility improved from -4.55±0.51 to -2.65±0.61 (t=-15.13, P<0.001) after 6mo postoperatively. CONCLUSION: PRT is an effective treatment for complete paralytic strabismus due to single rectus muscle palsy, and can achieve stable clinical efficacy.