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P. Ekstrom, T. Talukdar, F. Paquet–Durand, L. Johnson, T. van Veen; Poly(ADP–Ribose) Polymerase (PARP) Is Activated in Degenerating Photoreceptors of the Rd1 Mouse . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1423.
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© ARVO (1962-2015); The Authors (2016-present)
The rd1 mouse retina represents a model system for Retinitis Pigmentosa, and suffers from an inherited mutation that leads to an early and rapid degeneration of the photoreceptors. The degeneration occurs via apoptosis but in contrast to many other examples of apoptotic cell death, the rd1 photoreceptors die in a caspase independent way. Poly(ADP–ribose) polymerase (PARP) is a prominent nuclear protein, that is involved in DNA repair mechanisms. However, recent findings reveal that PARP, when overactivated, may actually contribute to cell death and thus take part in caspase independent apoptosis, such as in the rd1 retina. The present study therefore examined the activity of PARP in the degenerating rd1 retina and compared it to the wild type (WT) situation.
Retinas were collected from either rd1 or WT background C3H mice at various ages, fixed, cryo–sectioned and immunofluorescently labelled using primary antibodies towards either PARP or its enzymatic product, poly(ADP–ribose) (PAR). In addition, an in situ enzymatic assay was used on unfixed histological sections to reveal PARP activity at the cellular level. Various other antibodies and staining reagents were also used for colabelling with PAR immunostaining as well as PARP activity.
The PARP enzyme was present in most or all nuclei of both inner and outer retina neurons, without any readily observable differences between rd1 and WT preparations. By contrast, staining for the PARP product, PAR, demonstrated a clear signal in many rd1 photoreceptor nuclei in the rd1 retina, but none in the WT counterpart, at postnatal days (PN) 9–13 when photoreceptor degeneration is considerable. This was corroborated by the PARP in situ assay, which similarly labelled photoreceptors in the rd1 retina only. Colabelling showed that PAR staining overlapped with PARP activity but also with TUNEL labelling of apoptotic nuclei in rd1 photoreceptors.
PARP was present in all photoreceptor nuclei of both rd1 and WT retinas but only activated in the rd1 photoreceptors when these carried signs of degeneration. This could indicate that activation of PARP is an important step in the apoptotic process of photoreceptors suffering from certain forms of inherited degeneration.
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