Müller glia partially dedifferentiate but fail to reenter the cell cycle when photoreceptor degeneration is confined to loss of UV cones.
(A) Immunochemistry with double cone marker, zpr1 (magenta) in retinal cryosection of light-lesioned mi2004 fish with inducible nGFP (green) at 3 dpl; ON, optic nerve. Muller glia in dorsal (D) peripheral retina, where zpr1+ double cones are not destroyed by the intense light (bracket), re-express the nGFP reporter. Immature Muller glia at the ventral (V) margin adjacent to the CMZ express nGFP (arrow). (B) Immunocytochemistry for PCNA (magenta) in a retinal cryosection. PCNA+ neurogenic clusters at 3 dpl in the central retina where all cone subtypes are destroyed (asterisks). Inset, higher magnification of the boxed region. Progenitors in the CMZ are PCNA+ (arrows). (C) Whole, flat-mounted retina of light-lesioned (3 dpl) Tg(sws1:GFP;sws2:mCherry) fish. Blue (red) and UV cones (green) and red-green double cones (not shown) are missing in the central lesioned region bounded by dotted lines. UV cones (green) are ablated from most of the retina, including dorsal. (D) By 42 dpl both UV cones (green) and blue cones (red) have regenerated within the central region (dotted line). UV cones fail to regenerate in the regions where blue cones (along with red/ green double cones, not shown) were spared: Boxed area dorsal to the lesion shown at higher magnification in the upper right, shows organized rows of surviving blue cones (red), but very few UV cones (green). Regenerated cones in central retina are identifiable because they fail to recreate the precisely organized cone mosaic pattern (boxed area in lower right; also see Supplementary Figure S5). Scales: 100 μm, A, B; 200 μm C, D; 20 μm, D (high magnification).
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