A modified 3D stereophotogrammetry-based distraction test for assessing lower eyelid tension.

AIM: To investigate the reliability of a modified three-dimensional distraction test (3D-DT) and three-dimensional pinch test (3D-PT) for assessing lower eyelid tension (LET). METHODS: A cross-sectional study was conducted among 97 volunteers including 97 eyelids with no history of trauma, tumor, or reconstructive surgeries. Six three-dimensional photographs were acquired for each participant, including two photographs obtained in a neutral position (NP), two using a modified 3D-DT with a 15.9-grammes stainless steel eyelid hook performed, and two using 3D-PT. RESULTS: The mean absolute differences between NP, 3D-DT, and 3D-PT measurements varied between 0.07 and 7.42, 0.10 and 13.10, and 0.07 and 15.97, respectively; technical error of measurement varied between 0.05 and 7.81, 0.09 and 10.19, and 0.07 and 12.47, respectively; and relative error measurements varied between 0.10% and 11.50%, 0.16% and 30.51%, and 0.11% and 38.75%, respectively. For intra-rater reliability, the intraclass correlation coefficients (ICCs) were more than 0.80 in seven out of eight measurements obtained in the NP and 3D-DT, whereas those obtained in the 3D-PT were as low as less than 0.30 by rater 1; the ICCs of all the measurements obtained in all the positions (NP, 3D-DT, and 3D-PT) were more than 0.80 by rater 2. For inter-rater reliability six out of eight NP and 3D-DT measurements had an ICC greater than 0.80, whereas those of 3D-PT measurements were less than 0.30. For intra-method reliability, the ICCs of all the NP measurements were more than 0.87, whereas those of the six 3D-DT measurements and four 3D-PT measurements were more than 0.80. CONCLUSION: Our study results prove that the modified 3D-DT, which involves the use of an eyelid hook, can be a highly reliable method for evaluating LET. Furthermore, this novel and simple method may be utilized as the basis for further investigation and routine pre- and postoperative clinical evaluation.

Gene therapy conversion of striatal astrocytes into GABAergic neurons in mouse models of Huntington's disease.

Huntington's disease (HD) is caused by Huntingtin (Htt) gene mutation resulting in the loss of striatal GABAergic neurons and motor functional deficits. We report here an in vivo cell conversion technology to reprogram striatal astrocytes into GABAergic neurons in both R6/2 and YAC128 HD mouse models through AAV-mediated ectopic expression of NeuroD1 and Dlx2 transcription factors. We found that the astrocyte-to-neuron (AtN) conversion rate reached 80% in the striatum and >50% of the converted neurons were DARPP32+ medium spiny neurons. The striatal astrocyte-converted neurons showed action potentials and synaptic events, and projected their axons to the targeted globus pallidus and substantia nigra in a time-dependent manner. Behavioral analyses found that NeuroD1 and Dlx2-treated R6/2 mice showed a significant extension of life span and improvement of motor functions. This study demonstrates that in vivo AtN conversion may be a disease-modifying gene therapy to treat HD and other neurodegenerative disorders.

Chemical Conversion of Human Fetal Astrocytes into Neurons through Modulation of Multiple Signaling Pathways.

We have previously developed a cocktail of nine small molecules to convert human fetal astrocytes into neurons, but a nine-molecule recipe is difficult for clinical applications. Here, we identify a chemical formula with only three to four small molecules for astrocyte-to-neuron conversion. We demonstrate that modulation of three to four signaling pathways among Notch, glycogen synthase kinase 3, transforming growth factor ß, and bone morphogenetic protein pathways is sufficient to change an astrocyte into a neuron. The chemically converted human neurons can survive >7 months in culture, fire repetitive action potentials, and display robust synaptic burst activities. Interestingly, cortical astrocyte-converted neurons are mostly glutamatergic, while midbrain astrocyte-converted neurons can yield some GABAergic neurons in addition to glutamatergic neurons. When administered in vivo through intracranial or intraperitoneal injection, the four-drug combination can significantly increase adult hippocampal neurogenesis. Together, human fetal astrocytes can be chemically converted into functional neurons using three to four small molecules, bringing us one step forward for developing future drug therapy.

Rapid Antidepressant Effect of Hydrogen Sulfide: Evidence for Activation of mTORC1-TrkB-AMPA Receptor Pathways.

AIMS: We asked whether hydrogen sulfide (H2S), as the third gaseous mediator, provided fast antidepressant effect on major depressive disorders and underlying mechanisms. RESULTS: The decreased level of H2S was detected in the hippocampus of chronic unpredictable mild stress (CUMS)-treated rats. Acute administration of H2S either by H2S inhalation or by the donor NaHS produced a rapid antidepressant-like behavioral effect. Further investigation demonstrated that this effect of H2S was mediated by reversing the CUMS-induced decrease in dendritic spine density and required the activation of mammalian target of rapamycin (mTOR)C1 and neurotrophic TrkB receptors, which proceeded to increase synaptic protein expression, including postsynaptic density protein 95, synaptophysin, and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor GluR1/2 subunit. INNOVATION: This study provides the first direct evidence for detecting the decreased H2S in hippocampus of CUMS rats and the biological significance of H2S in treating major depression. CONCLUSION: Our data demonstrate that H2S activates mTORC1 signaling cascades and thereby produces fast-onset antidepressant effect. The study provides a profound insight into H2S or its donors as potent preventive and therapeutic agents for intervention of depression. Antioxid. Redox Signal. 27, 472-488.