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K. U. Loeffler, B. G. Kennedy, J. Mest, C. Strack, F. G. Holz, K. C. Cheng, N. J. Mangini; Morphologic Changes in Retinal Pigment Epithelium (RPE) of the Hypopigmented Zebrafish Mutant, Golden (golb1). Invest. Ophthalmol. Vis. Sci. 2007;48(13):1221. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
The zebrafish mutant, golden, is hypopigmented due to a mutation in a novel cation exchanger, NCKX5 (SLC24A5). Pigmentation has been shown, at least epidemiologically, to be an important factor in age-related macular degeneration (AMD). In addition, NCKX5 has been demonstrated in human RPE, and the gene encoding NCKX5 is located on chromosome 15q21, a region that also has a major susceptibility locus associated with AMD. The aim of this study is to evaluate the morphologic features of the retina/RPE of the golden zebrafish in comparison with human AMD in order to establish a possible animal model for this disease.
Wildtype (Lyles) and mutant (golden, golb1) zebrafish (sacrificed in light) were fixed in paraformaldehyde or glutaraldehyde. Eyes were removed and investigated by light (LM) or electron microscopy (EM), respectively. 22 eyes were obtained from wildtype (wt), age range 8-34 months, and 18 from golden, age range 9-33 months.
By LM, there was an obvious difference in pigmentation of the RPE between wt and golden. In wt zebrafish, younger eyes revealed densely pigmented RPE cell bodies that appeared to become somewhat less pigmented with increasing age. Apical processes in younger eyes were also heavily pigmented throughout up to the nuclear layer while in adult eyes pigmentation was concentrated around the cones. Eyes of golden zebrafish even at the youngest age had only lightly pigmented RPE cell bodies with easily visible nuclei. With increasing age, the RPE cytoplasm appeared more granular. In all eyes (wt and golden) round, heavily-pigmented structures were identified above the RPE nuclear layer, with an obvious increase with age within the wt RPE (0.4 to 3.8 /section) but only a slight increase in golden RPE (0.38 to 1.7 /section). By EM, these bodies could be identified as cells containing ovoid to longish melanolipofuscin-like granules obviously originating from the RPE. Melanosomes of close-by choroidal cells contained distinctly different granules and showed no obvious difference in number between wt and golden. At the LM level, no obvious difference between wt and golden was evident in any other ocular tissue.
These results demonstrate a definite difference in retinal morphology between wildtype and golden zebrafish that changes with age. Further studies are warranted to establish the precise time course of these alterations and to evaluate in more detail the impact of this particular NCKX5 mutation within the eye.
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