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Ying Chen, David J orlicky, David C Thompson, Vasilis Vasiliou; Glutathione Plays a Novel and Critical Role in Ocular Surface Development. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5720.
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© ARVO (1962-2015); The Authors (2016-present)
Glutathione (GSH) maintains cellular redox balance and acts as a redox-signaling molecule. Although GSH is actively synthesized in the developing eye at both embryonic and early postnatal stages and is present at high millimolar levels in ocular surface tissues, its role in ocular morphogenesis remains to be elucidated. The purpose of the current study is to explore the role of GSH in the development of ocular surface tissues.
We developed GclcLe/Le mice, a strain in which GSH biosynthesis is selectively abolished in surface ectoderm-derived ocular structures. Gross morphology and histology of eye tissues were performed at embryonic day (ED) 15, and post-natal days (PD) 1, 21 and 50.
GclcLe/Le embryos at ED15 had normal development of ocular surface tissues, including lens, cornea, conjunctiva, and eyelids. At early postnatal stage (PD 1 and 21), GclcLe/Le mice exhibited bilateral small eyes (microphthalmia) by PD21, whereas the eyes of Gclcw/Le heterozygotes appeared grossly normal at this same stage. Histological examination revealed both eyes of GclcLe/Le mice to have defective lens featuring poor differentiation and vacuolation of fiber cells. This change was noted only in the right eyes of Gclcw/Le heterozygotes. Other ocular surface structures appeared unaffected in either GclcLe/Le or Gclcw/Le mice. In adult mice (PD50), GclcLe/Le eyes were completely closed, whereas Gclcw/Le heterozygotes showed unilateral small eye on the right side. Anterior ocular structures in affected eyes, including lens, cornea, cillary body and iris, had histological abnormalities primarily featuring hypercellularity, poor differentiation and apoptotic cell death.
These results demonstrate a novel and critical role for GSH in perinatal lens maturation and postnatal maintenance of the ocular surface. Redox proteomics analyses are currently being used to determine the mechanism by which GSH controls eye development.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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