Purchase this article with an account.
Knut Stieger, Jutta Ulrike Schlegel, Dorothee Röll, Brigitte Müller, Baerbel Fuehler, Birgit Lorenz; In vivo and post mortem analysis of the outer retina and RPE in a mouse model for X-linked retinitis pigmentosa. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1720.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Mutations in the Retinitis pigmentosa GTPase regulator (RPGR) are associated with X-linked Retinitis pigmentosa (XLRP) and account for up to 20% of all RP cases. No treatment option exists to date. The aim of this study is to analyse morphological alterations in the outer retina and RPE of a new mouse model for XLRP in vivo and post mortem in order to further decipher the pathomechanism of the disease.
A mouse model for XLRP was generated by introducing a pathological mutation (2793delA), two silent mutations (3071subT-A; 2650subT-C), as well as an ISceI recognition site into C57BL6/129sv hybrid embryonic stem cells through homologous recombination and breeding of the chimeric animals into a C57BL/6J background. Time points for the analysis were 1, 3, 6, 9, 12, 15, and 18 months of age (M). Animals were examined in vivo by optical coherence tomography (OCT) and funduscopy (MICRON III System, Phoenix Research Inc.) in the peripapillary area and in the periphery. Post mortem analysis included Hematoxylin/Eosin (H/E) staining of paraffin sections, immunofluorescence staining (L/M-opsin, S-opsin, centrin, RPGR) and electronmicroscopy (EM) analysis.
OCT examinations revealed reduced visibility of the outer retinal layers including the inner segment ellipsoid (Ise), and outer segments as early as at 3 M in affected as well as carrier animals, while the ONL thickness only decreased starting at 12 M. Focal white spots were visible on the fundus image at 3 M. Interestingly, these alterations were more pronounced in carriers. Post mortem analysis showed progressive disorganisation of inner and outer segments of the photoreceptors starting at 1 M and a reduction in the number of photoreceptor nuclei starting at 12 M. Altered connecting cilium structure and reduced opsin transport was visible early in the disease process.
The newly generated mouse model shows early onset of morphological alterations in the outer retina and RPE, which can be visualized and quantified in vivo as well as post mortem. Since the model has been designed specifically for studying new therapeutic approaches in XLRP treatment, these morphological biomarkers can now be used to analyse a possible treatment effect.
This PDF is available to Subscribers Only