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Ying Chen, Nicholas Apostolopoulos, David Orlicky, David M.G. Anderson, Kevin L Schey, David Thompson, Richard A Lang, Vasilis Vasiliou; Glutathione is Required for Ocular Surface Development. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1724.
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Glutathione (GSH) maintains cellular redox balance and acts as a redox-signaling molecule. It is actively synthesized at millimolar levels in the developing eye during embryonic and early postnatal stages. The current study tests the hypothesis that GSH plays a pivotal role in the development of ocular surface.
We developed GclcLe/Le mice, a strain in which GSH biosynthesis is selectively abolished in surface ectoderm-derived ocular structures. Histology of eye tissues were examined at embryonic day (ED) 15, and post-natal days (PND) 1, 21 and 50. The ocular phenotypes were further characterized by Imaging Mass Spectrometry (IMS) and gene expression analysis around PND25.
GclcLe/Le embryos at ED15 had normal development of ocular surface tissues, including lens, cornea, conjunctiva, and eyelids. At birth (PD1), GclcLe/Le mice show defective lens featuring poor differentiation and vacuolation of fiber cells. Abnormalities in other ocular structures, including the cornea and retina, were not observed until PD21. GclcLe/Le mice exhibited bilateral small eyes (microphthalmia) by PD21. IMS examination of the whole eyes around this age revealed distinct changes in the lipid and protein profiles in the GclcLe/Le ocular tissues relative to control eyes. Panels of genes involved in regulation of eye development (SOX2 and SIX3), signal transduction (NOTCH1, CATNB and FGF7) and stress response (PTEN, NRF2, and HMOX1) were found to be differentially altered in a tissue-specific manner in GclcLe/Le eyes.
Our results show that GSH plays a critical role in ocular development, likely by regulating multiple molecular pathways. Further studies are underway to identify molecular details involved in this process.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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