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Jin Wan, Daniel Goldman; Fgf8a regulates Müller glia proliferation in the uninjured and injured retina. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5401.
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The teleost retina grows throughout life and exhibits a robust regenerative response following injury. Critical to both these events are Müller glia (MG) that divide and generate progenitors for retina growth and repair. Here, we report that Fgf8a is a MG niche factor that regulates both spontaneous and injury-dependent MG proliferation.
Eye lesions were performed by needle poke. Dividing cells were labeled with BrdU. RT-PCR was combined with in situ hybridization to identify the expression of fgf8a RNA following injury. hsp70:fgf8a transgenic fish were used to conditionally express Fgf8a with heat shock. Tp1:mCherry fish were used to report Notch signaling.
In the uninjured retina, fgf8a RNA is expressed in cells residing in the inner nuclear layer. Following retinal injury, fgf8a is rapidly suppressed in a pan-retina fashion and returns by 2 days post injury (dpi). Heat shock of hsp70:fgf8a transgenic fish showed Fgf8a inhibits injury-dependent MG proliferation of older fish retinas, while stimulating MG proliferation in younger fish retinas. Using Tp1:mCherry fish, we found that Fgf8a mediates its effects on MG proliferation by controlling Notch signaling. These transgenic fish revealed Notch signaling is active in quiescent MG and inhibited in proliferating MG. Remarkably, the effects of Fgf8a on Notch signaling switches as MG age from 2-4 month.
Our studies identify a remarkable plasticity in Fgf8a signaling that may underlie spontaneous and injury-dependent MG proliferation in the uninjured and injured retina. Furthermore, we uncovered a switch in Fgf8a signaling as MG age, which may contribute to age-related differences in spontaneous MG proliferation and help define proliferative and quiescent MG niches.
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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