postdoctoral researcher, UC Berkeley, Vision Science
Know more about anatomy and function of tissue, know more ways help people.
Myopia, nearsightedness, is a clinically common refractive error. Although myopic refractive errors can be corrected by lenses or surgery, these add more economic burden to the family and society, and the onset of myopia is shifting to younger ages, now even affecting preschoolers, who are spending increasing time hunched over computers and other electronic gadgets. The worst consequence of an earlier myopia onset is more high myopia, which increases the risk of ocular diseases – including cataract, glaucoma, retinal detachment, and myopic macular degeneration, all of which can cause irreversible vision loss. Identifying genetic susceptibility factors (e.g., eye shape, choroidal thickness perhaps), and environmental risk factors (e.g., extended near-work, limited outdoor activity), will help us to develop strategies for more effectively controlling myopia development – to delay myopia onset and/or retard myopia progression, and so ultimately decrease the blindness associated with pathologic myopia. Using animal models can help to clarify the roles of environmental conditions in causing myopia and lead to better preventive measures. We have reported that two strains of pigmented guinea pigs vary significantly in their sensitivity to myopia-inducing stimuli (negative lenses and form deprivation); one strain, with a thicker choroid, responded in opposite ways to +5D and -5D lenses. Imaging in vivo showed that, while the overall choroidal thickness was similar across pigmented strains, the detailed structure of the choroid was significantly different. My hypothesis is that the structure of the choroid determines its functional responses to the same myopiagenic stimuli. The mechanism underlying this difference, and its contribution to myopia control, will be investigated in depth. Similar differences in choroidal thickness in humans might contribute to individual differences in their susceptibility to myopia.
Abstract: An imbalance between oxidative stress and antioxidant activity plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Cigarette smoke, a major risk factor of COPD, induces cellular oxidative stress, but levels of antioxidants such as heme oxygenase-1 (HO-1) are reduced in individuals with severe COPD. In this study, we evaluated the molecular mechanism of reduced HO-1 expression in human bronchial epithelial cells. We found that cigarette smoke extract (CSE) increases HO-1 levels via activation of NFE2-related factor 2 (Nrf2). However, pretreating cells with the protease neutrophil elastase (NE) suppressed the CSE-induced expression of HO-1 mRNA and protein. NE also decreased sirtuin 1 (SIRT1) level, but did not inhibit CSE-induced nuclear translocation and DNA-binding activity of Nrf2. Transfection of cells with a Myc/His-tagged SIRT1 expression vector completely blocked the NE-mediated suppression of HO-1 expression. We further noted that the NE-induced downregulation of SIRT1 was not due to decreased transcription or proteasomal/lysosomal degradation or loss of solubility. Immunofluorescence staining revealed that NE enters the cell cytoplasm, and we observed that NE directly cleaved SIRT1 in vitro, indicating that SIRT1 levels are decreased via direct degradation by internalized NE. Of note, we observed decreased SIRT1 levels in NE-treated primary human bronchial epithelial cells and in lung homogenates from both smokers and patients with COPD. In conclusion, NE suppresses CSE-induced HO-1 expression by cleaving SIRT1. This finding indicates the importance of cross-talk between oxidative stress and protease responses in the pathogenesis of COPD.
Pub.: 08 Jun '17, Pinned: 16 Jun '17
Abstract: To understand complex biological systems requires the integration of experimental and computational research -- in other words a systems biology approach. Computational biology, through pragmatic modelling and theoretical exploration, provides a powerful foundation from which to address critical scientific questions head-on. The reviews in this Insight cover many different aspects of this energetic field, although all, in one way or another, illuminate the functioning of modular circuits, including their robustness, design and manipulation. Computational systems biology addresses questions fundamental to our understanding of life, yet progress here will lead to practical innovations in medicine, drug discovery and engineering.
Pub.: 15 Nov '02, Pinned: 16 Jun '17