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A. Maass, A. L. Georgiou, T. E. Salt, M. F. Cordeiro; Investigating Retinal Ganglion Cell Changes in the RCS Rat - A Model of Retinal Dystrophy. Invest. Ophthalmol. Vis. Sci. 2007;48(13):243.
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© ARVO (1962-2015); The Authors (2016-present)
The RCS rat is a model of retinal dystrophies such as human retinitis pigmentosa (RP) where the loss of retinal photoreceptors has been well documented. The natural history of changes in retinal ganglion cells (RGC) in this model however is less well established. The aims of this study were to investigate the development of RGC apoptosis and loss, assess RGC function and correlate this with changes in intraocular pressure in the RCS rat.
All investigations were performed on dystrophic RCS rats and age-matched non-dystrophic controls (at 1, 2, 3, 6, 9, 12, 18 and 24 months of age with at least n=3 animals per age group). In vivo retinal images were recorded and RGC apoptosis assessment was performed using fluorescent labeled Annexin V and the DARC (detection of apoptotic retinal cells) technique in vivo with histological analysis performed thereafter, using methods we have previously described. Scotopic ERGs were recorded with averages of 40 -80 single flash presentations per intensity (80 for the dimmest and 40 for the higher intensities) and analysed. IOP was measured in both eyes of each animal using a Tono-pen - 10 readings were obtained for each eye and then averaged.
RGC apoptosis counts from confocal histology revealed an age-related effect with peak apoptosis occurring at 6 months of age (p<0.05) compared to control. ERG analysis showed a decrease in both STR and b-wave amplitudes at 3 months of age compared to control (p<0.05). IOP measurements show elevated values from 3-12 months of age with peak IOP (26.4-8 mmHg) at 6 months of age compared to control animals. Finally, there was evidence of thinning of the retinal nerve layer in the older RCS rats.
Our study clearly shows RGC damage in the RCS rat earlier than previously reported. Peak RGC apoptosis was documented at 6 months with abnormal RGC function recorded even earlier at 3 months of age. The elevated IOP profile found in this study is very similar to that found in transgenic models of secondary glaucoma. We believe that the RGC loss in the RCS rat might be linked to an increase in IOP, which may occur in addition to RGC degeneration secondary to photoreceptor loss. An understanding of the mechanisms leading to ganglion cell loss and the evaluation of time points before vision loss occurs in diseases such as Retinitis Pigmentosa is essential for the design of much-needed therapeutic strategies to save sight.
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