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Daniel Sun, Sara Moore, Tatjana C Jakobs; STAT3-mediated astrocyte reactivity within the optic nerve head preserves visual function.. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3737.
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© ARVO (1962-2015); The Authors (2016-present)
Reactive remodeling of astrocytes within the optic nerve head is observed in glaucoma and virtually all other optic nerve injuries. The mechanism and function of this reactivity is not well known. Is it beneficial or harmful for overall visual function?
We used a loss- and gain-of-function study to either attenuate or enhance astrocyte reactivity during experimental glaucoma and nerve crush, and then determined the effects on various histological and functional outcome measures. Reactivity was attenuated by conditional knockout of the transcription factor signal transducer and activator of transcription 3 (STAT3) from astrocytes using the Cre-loxP system under regulation of the mouse glial fibrillary acidic protein promoter. Reactivity was enhanced by knocking out suppressor of cytokine signaling 3 (SOCS3), the negative feedback molecule of STAT3. Visual function was assessed using the electroretinogram and optokinetic response.
Following injury, STAT3 knockout mice displayed attenuated astrocyte hypertrophy and reactive remodeling, compared to controls. These changes were associated with significantly increased loss of ganglion cells and visual function over a 30-day period. In contrast, SOCS3 knockout mice showed improved survival of ganglion cells and visual function.
The STAT3 signaling pathway is an important mediator of various aspects of the reactive phenotype. Reactive astrocytes have a protective role early in glaucoma, preserving visual function.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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