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Gustavo D. Aguirre, Ágnes I. Berta, Sem Genini, William A. Beltran; Photoreceptor Cell Mitosis Preserves Outer Nuclear Layer During the Peak of Cell Death in the STK38L Mutant Dog Retina. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1840.
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© ARVO (1962-2015); The Authors (2016-present)
Early retinal degeneration (erd) is an autosomal recessive early onset canine retinal degeneration caused by a mutation in the STK38L gene. In mutants, abnormal development is followed by degeneration of rods and cones. We previously showed that TUNEL-, and PCNA-labeled cells were present in the erd ONL, but did not establish that labeling represented independent events, and did not exclude that PCNA labeling was associated with DNA damage or repair. We now have used phospho histone-H3 (PHH3) labeling to determine if photoreceptor mitosis is occurring in the early stages of degeneration.
Paraformaldehyde fixed retinas from affected and controls dogs (ages 4-14 wks), were embedded in OCT. Cell death was assessed by TUNEL, mitosis and cell proliferation by PHH3 and PCNA labeling. Expression of rod, cone, Müller cell and stem cell-specific markers was examined by immunocytochemistry using conventional and confocal fluorescence microscopy.
Photoreceptor cell death and mitosis was sustained between 7-14 wks. Dual labeling with PHH3 and TUNEL demonstrated that both processes occurred concurrently in the ONL, but involved different cells. The PHH3- and PCNA-labeled cells also expressed rod opsin. Müller cells did not label with PHH3 or PCNA, and comparable nestin labeling of neuronal stem cells was limited to the ciliary marginal zone in control and mutant retinas. Coincident with photoreceptor mitosis is a change in the photoreceptor mosaic. Prior to cell death/mitosis the photoreceptor mosaic is composed of L/M- and S-cones, and rods. After mitosis, both cone types remain, but the majority of rods are hybrid photoreceptors that express rod opsin and, to a lesser extent, cone S-opsin.
The erd-mutant retina appears to be unique in showing a burst of photoreceptor mitosis in the ONL that parallels the time window for cell death. During this time period, the photoreceptor population changes, and hybrid rod/S-cones are the predominant cell class.
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