Fig. 4

Co-operation of oncogenic GNAQ^Q209P and p53 loss-of-function results in UM development. Oncogenic GNAQ^Q209P Tol2 construct was injected into p53-deficient (p53^M214K/M214K) zygotes, animals were sacrificed at 2 and 5 months or sooner if ocular protrusion was prominent, then fixed eye specimens were processed and paraffin-embedded for transverse sectioning at a thickness of 5 μm, followed by H&E staining. Representative images are shown. A.I. A non-injected p53-deficient (p53^M214K/M214K) control zebrafish illustrating a single layer of choroidal melanocytes. B.I. Benign choroidal hyperplasia in an 8-week-old Tg (mitfa:GNAQ^Q209P;p53^M214K/M214K) zebrafish. Note the diffuse thickening of the entire choroid caused by the proliferation of choroidal melanocytes. Nuclear and plexiform layers of the retina, photoreceptors layer, and RPE are structurally normal. Also, sclera is respected, with no evidence of infiltration or perforation. C.I. An example of malignancy, with non-pigmented hyperproliferative atypical cells developing within an area that shows evidence of choroidal hyperplasia in a 20-week-old Tg (mitfa:GNAQ^Q209P;p53^M214K/M214K) zebrafish. D.I. A second example of a 20-week-old Tg (mitfa:GNAQ^Q209P;p53^M214K/M214K) zebrafish developing an eye malignancy infiltrating the ciliary body, iris, and cornea, also with evidence of choroidal hyperproliferation. A.II, B.II, C.II, D.II. Magnifications of the regions within the white dashed boxes in A.I, B.I, C.I, D.I, respectively, illustrating the changes within the choroidal melanocyte layer (B.II, C.II, D.II), as compared to a structurally normal choroid in a non-injected control (A.II). (C.III, D.III) Magnifications of transformed uveal melanocytes depicted in the black dashed boxes in C.I and D.I, respectively. Abbreviations: RPE, retinal pigmented epithelium. Scale bar lengths, as indicated.