Soluble CX3CL1 gene therapy improves cone survival and function in mouse models of retinitis pigmentosa
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Authors: Wang, Sean K.; Xue, Yunlu; Rana, Parimal; Hong, Christin M.; Cepko, Constance L.
Abstract
Retinitis pigmentosa (RP) is a disease that initially presents as night blindness due to genetic deficits in the rod photoreceptors of the retina. Rods then die, causing dysfunction and death of cone photoreceptors, the cell type that mediates high acuity and color vision, ultimately leading to blindness. We investigated immune responses in mouse models of RP and found evidence of microglia activation throughout the period of cone degeneration. Using adeno-associated vectors (AAVs), delivery of genes encoding microglial regulatory signals led to the identification of AAV serotype 8 (AAV8) soluble CX3CL1 (sCX3CL1) as a promising therapy for degenerating cones. Subretinal injection of AAV8-sCX3CL1 significantly prolonged cone survival in three strains of RP mice. Rescue of cones was accompanied by improvements in visual function. AAV8-sCX3CL1 did not affect rod survival, microglia localization, or inflammatory cytokine levels in the retina. Furthermore, although RNA sequencing of microglia demonstrated marked transcriptional changes with AAV8-sCX3CL1, pharmacological depletion of up to similar to 99% of microglia failed to abrogate the effect of AAV8-sCX3CL1 on cone survival. These findings indicate that AAV8-sCX3CL1 can rescue cones in multiple mouse models of RP via a pathway that does not require normal numbers of microglia. Gene therapy with sCX3CL1 is a promising mutation-independent approach to preserve vision in RP and potentially other forms of retinal degeneration.
Multi-stress radioactive-tolerant Exiguobacterium acetylicum CR1 and its applicability to environmental cesium uptake bioremediation
JOURNAL OF CLEANER PRODUCTION
Authors: Oh, Seo Yeong; Heo, Nam Su; Shukla, Shruti; Kang, Sung-Min; Lee, Ilsong; Lee, Hoomin; Bajpai, Vivek K.; Jang, Sung-Chan; Han, Young-Kyu; Roh, Changhyun; Huh, Yun Suk
Abstract
Several industries using gamma sterilization techniques for food safety, and long shelf-life purposes. Nuclear energy production has increased the amount of spent nuclear fuel produced, which poses risks of severe diseases in human. Cesium is one of the most hazardous material can cause human exposure to air, water, and food. The efficient removal of cesium ions (Cs+) has been emphasized using biological control strategies. In this study, we isolated a new Cs+-tolerant (100, 500, and 750 ppm) and gamma radiation resistant (1, 3, and 5 kGy) soil bacterium (CR1) from the soil around a nuclear power plant in Korea, which was identified as Exiguobacterium acetylicum CR1 by 16S rRNA sequencing. E. acetylicum CR1 was found to be resistant to high doses of gamma radiation without any loss in Cs+ tolerance or survival. Furthermore, E. acetylicum CR1 was found to act as a microbiological control agent with respect to the removal of cesium from contaminated water. Interestingly, after gamma radiation exposure, E. acetylicum CR1 developed significantly (p < 0.05) greater Cs+ bio-sorption capacity than non-irradiated control cells (24.63+/-0.02% vs. 12.54+/-0.06%), which confirmed that gamma radiation had no negative impact on its ability to remove Cs+ or on its growth/survival. The ability of E. acetylicum CR1 to adsorb Cs+ from contaminated water samples or radioactive environmental waste suggests it has broad spectrum potential as an environmentally friendly remedial tool in the contexts of soil ecology, agriculture, crop management, food, and medicine. (C) 2018 Elsevier Ltd. All rights reserved.