Perceptual learning for treating amblyopia in children based on activation of visual signal pathway Relationship of curative effects and time

BACKGROUND： Conventional methods （such as occlusion therapy, fine manipulation, complementary, and alternative medicine） take effects slowly, are time and labor consuming, and have uncertain curative effects in the treatment of amblyopia. Perceptual learning, a new method for treating amblyopia, improves the ability to process signals from the cerebral optic nerve system by specific visual stimulation and visual learning, as well as activation of the visual signal pathway utilizing brain nervous system plasticity. OBJECTIVE： This study investigated and evaluated the curative effects of perceptual learning, which can directionally increase brain plasticity, on the treatment of amblyopia in children. The relationship between curative effect and time was also analyzed. DESIGN： A self-control experiment. SETTING： Visual Science and Optometry Center, People＇s Hospital of Guangxi Zhuang Autonomous Region. PARTICIPANTS： A total of 125 amblyopic children （250 amblyopic eyes）, 73 males, 52 females, averaging （6±2） years of age, received treatment at the Visual Science and Optometry Center, People＇s Hospital of Guangxi Zhuang Autonomous Region between September 2006 and February 2007 and were recruited for this study. All children presented with no structural disease of the eyeballs. Written informed consent for therapeutic regiments was obtained from each child＇s parent. The protocol received approval from the Hospital＇s Ethics Committee. METHODS： Visual function was tested with a perceptual learning system （Research Center for Human Health and Development of Sun Yat-sen University, National Engineering Technique Research Center for Medical Care Implement） for visual noise, position noise, contour discrimination, contrast sensitivity, grating stereogram, and random-dot fusion. These tests helped to evaluate the efficiency of visual information processing of these children, and to determine the degree of defects of the optic nerve cells and the connections of visual cortical neurons. According to results of visual function tests, individualized treatment was adopted for each amblyopia patient using perceptual learning system. One course of treatment lasted one month, and treatment was performed twice every day with two training procedures （each training procedure lasted for ten minutes）. There was a ten-minute time interval between the two training procedures. The training treatment was performed in a quiet and dark environment. Visual acuity and recovery of visual function were tested every month. Original training procedure was continued or adjusted according to the results of visual function. MAIN OUTCOME MEASURES： Visual function change; relationship of curative effects and curative time. RESULTS： A total of 125 amblyopia children were included in the final analysis. The total efficiency of perceptual learning for treating amblyopia in children was 75.2%. Visual acuity began to greatly increase 3 months after treatment （P 〈 0.05）. Visual acuity was best corrected from 0.60 ± 0.23 before treatment to 0.86 ± 0.26 after treatment （P 〈 0.05）. The mean time to reach improved levels with curative effects was （2.82 ± 1.30） months, and to reach a basically cured level was （2.87 ±1.40） months. Percentage of improved visual acuity was the highest [98% （39/40）] in children that received 3 months of treatment and the lowest [55% （31/56）] in children that received 1 month of treatment （P 〈 0.05）. The percentage of basically cured levels with curative effects increased with length of learning time and was the greatest in children that received 4 months of treatment [67% （31/46）, P 〈 0.05]. CONCLUSION： Perceptual learning rapidly and remarkably improves visual function of amblyopia children; however, the curative effects are first apparent two and three months after intervention.

Ocular Surface Characteristics and Impression Cytology in Patients with Active versus Inactive Thyroid Eye Disease

Purpose:To compare the clinical findings, tear film function and impression cytology between patients with active and inactive Thyroid Eye Disease (TED). Methods:.A total of 56 patients with TED and 30 controls were recruited in this prospective observational cohort study. TED patients were divided into active TED and inactive TED types according to a seven-point modified formulation of the Clinical Activity Score (CAS). All participants underwent full eye examinations including Ocular Surface Disease Index (OSDI) score, tear film break-up time (TBUT), fluorescein staining and Schirmer I test. Thirty nine patients with thyroid-associated orbitopathy.(TAO) received Nelson's grade with conjunctival impression cytology. Proptosis, palpebral fissure width and lagophthalmos were assessed. Results:.Ocular surface parameters including proptosis, palpebral fissure width and lagophthalmos did not differ between active and inactive TED patients(P>0.05). Both active and inactive TED patients obtained higher fluorescein staining scores, lower TBUT scores and significantly lower Schirmer test scores than those of controls (P<0.001 for all). Additionally, the TBUT score was significantly lower and the OSDI score significantly higher in the active TED group compared with those in the inactive TED group (P<0.001 for both). Impression cytology revealed a higher proportion of grade 2-3 changes in the active TED group compared with the inactive TED group(P<0.001). Conclusion:.Orbital inflammation in TED patients may lead to decreased tear film stability and ocular surface squamous metaplasia.

Effect of hypotonic medium on aquaporin-4 expression in cultured astrocytes

BACKGROUND： Aquaporin-4 （AQP4） is abundant in astrocytes, ependymal cells, and the choroid plexus, and is associated with cerebrospinal fluid formation and osmoregulation. AQP4 is speculated to be the hypothalamic osmoreceptor and regulator of water balance. OBJECTIVE： To examine AQP4 expression and its role in cultured rat astrocytes after exposure to hypotonic medium. DESIGN, TIME AND SETTING： Randomized control experiment. This experiment was carried out in the Research Room of Neurobiology, Chongqing University of Medical Science, China, between April and October 2003. MATERIALS： Two-day-old newborn Wistar rats （n =20）, weighing 10- 15 g, were purchased from the Experimental Animal Center of Chongqing University of Medical Science, China. METHODS： Purified rat cerebral cortical astrocytes were isolated fiom Wistar rats for in vitro cell culture experiments. The cells were randomly divided into control and hypotonic groups. The in vitro cell edema model was established by exposing astrocytes to hypotonic medium （268, 254, or 240 mmol/L）. Cells in the control group were cultured in normal culture medium. MAIN OUTCOME MEASURES： Morphological changes in astrocytes were observed under an inverted microscope and a transmission electron microscope after cells were cultured for 3, 6, 12, or 24 hours with hypotonic medium or normal culture medium. In each group, AQP4 protein and mRNA expression were assessed by immunocytochemistry, in situ hybridization, and reverse transcription polymerase chain reaction at the different time points. RESULTS： After astrocytes were cultured for 3, 6, 12, or 24 hours with hypotonic medium （268, 254, 240 mmol/L）, they showed typical features of cell edema. In the control group, no astrocytes developed pathological changes. There were no significant changes in the AQP4 mRNA and protein expression in the control group at any of the time points alter astrocytes were cultured with normal culture medium （P 〉 0.05）. Compared with the control group, AQP4 mRNA and protein expression in the hypotonic group were remarkably increased at all time points after astrocytes cultured with hypotonic medium （268, 254, 240 mmol/L; P 〈 0.05）. AQP4 mRNA and protein expression increased with increasing exposure time and with decreasing concentration of the hypotonic medium. CONCLUSION： Hypotonic medium induced cell edema and increased AQP4 mRNA and protein expression. Up-regulated expression of AQP4 was correlated with hypotonic medium concentration in a time dependent manner.

Association between peroxisome proliferator-activated receptor-γ coactivator-1α gene polymorphisms and type 2 diabetes in southern Chinese population:role of altered interaction with myocyte enhancer factor 2C

Background Some single nucleotide polymorphisms （SNPs） in the peroxisome proliferator-activated receptor-y coactivator （PGC）-1α gene have been reported to be associated with type 2 diabetes in different populations, and studies on Chinese patients yielded controversial results. The objective of this case-control study was to explore the relationship between SNPs of PGC-1α and type 2 diabetes in the southern Chinese population and to determine whether the common variants： Gly482Ser and Thr394Thr, in the PGC-1α gene have any impacts on interaction with myocyte enhancer factor （MEF） 2C. Methods The SNPs in all exons of the PGC-1α gene was investigated in 50 type 2 diabetic patients using polymerase chain reaction-single strand conformational polymorphism （PCR-SSCP） and direct sequencing. Thereafter, 263 type 2 diabetic patients and 282 healthy controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP）. A bacterial two-hybrid system and site-directed mutagenesis were used to investigate whether Gly482Ser and Thr394Thr variants in the PGC-1α gene alter the interaction with MEF2C. Results Three frequent SNPs （Thr394Thr, Gly482Ser and Thr528Thr） were found in exons of the PGC-1α gene. Only the Gly482Ser variant had a different distribution between diabetic patients and healthy subjects, with the 482Ser allele more frequent in patients than in controls （40.1% vs 29.3%, P〈0.01）. Even in controls, the 482Ser（A） carriers were more likely to have higher levels of total cholesterol and low-density lipoprotein cholesterol than the 482Gly（G） carriers. The 394A-482G-528A haplotype was associated with protection from diabetes, while the 394A-482A-528A was associated with the susceptibility to diabetes. The bacterial two-hybrid system and site-directed mutagenesis revealed that the 482Ser variant was less efficient than the 482Gly variant to interact with MEF2C, whereas the 394Thr （A） had a synergic effect on the interaction between 482Ser variant and MEF2C. Conclusions The results suggested that the 482Ser variant of PGC-1α conferred the susceptibility to type 2 diabetes in the southern Chinese population. The underlying mechanism may be attributable, at least in part, to the altered interaction between the different variants （Gly482Ser, Thr394Thr） in the PGC-1α gene and MEF2C.