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Vijay P Sarthy, V. Joseph Dudley, Jie Zhu, Deepak A Lamba; Withferin-A can modulate Müller cell gliosis in the mouse retina. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5392.
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© ARVO (1962-2015); The Authors (2016-present)
In response to injury or disease, Müller cells undergo ‘reactive gliosis’, which is accompanied by changes in their morphology, upregulation of various markers such as glial fibrillary acidic protein (GFAP), de-differentiation and sometimes proliferation. In the present study, we have investigated whether Müller cell gliosis can be modulated by the small molecule inhibitor, Withaferin-A (WFA).
Balb/c or 129S6 mice were pretreated with WFA by i.p. injection and exposed to 13K Lux light for 2 hr to induce photoreceptor degeneration and gliosis. Gliosis was monitored by examining GFAP expression in histological sections. In other experiments, 1-month old Crx-mutant mice were treated with WFA and gliosis was examined by determining changes in transcript levels for several gliosis-associated genes using qPCR. To examine the mechanism of WFA action, the Müller cell line, rMC-1, was treated with WFA and cell extracts were immunoblotted using anti-STAT3 antibody.
WFA pretreatment suppressed GFAP appearance in Müller cells in mice exposed to intense light. In the Crx-mutant mice, there was significant gliosis and intravitreal WFA injection resulted in a 2 to 4-fold reduction in transcript levels for the gliosis-markers -- CD44, Gfap, Lgals3 and S100b. Interestingly, GFAP expression in histological sections was not significantly altered in WFA treated mice. Finally, immunoblotting analysis indicated that pSTAT3 level was significantly lower in WFA treated Müller cells.
WFA can suppress Müller cell gliosis associated with induced- or inherited- photoreceptor degeneration. WFA suppresses Müller cell gliosis by blocking activation of the JAK/STAT signaling pathway.
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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