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V. Porciatti, M. Tapia, R.K. Lee; Age–Related Changes of the Pattern Electroretinogram in the DBA/2J Mouse Model of Glaucoma . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4011.
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© ARVO (1962-2015); The Authors (2016-present)
The use of mouse models of glaucoma is currently limited by the lack of non–invasive measurements able to monitor retinal ganglion cell (RGC) dysfunction. Our purpose was to characterize the progressive loss of electrical activity of RGCs by means of the Pattern Electroretinogram (PERG) in the DBA/2J mouse model of glaucoma with spontaneously elevated intraocular pressure.
PERGs were recorded from 60 undilated eyes of anesthetized (Ketamine–Xylazine) DBA/2J mice of different ages (range 1.5–14 months, mean 6.25 ± 3.4 months) in response to contrast–reversal of gratings that maximize PERG amplitude (95% contrast, 1 Hz reversal, 0.05 cycles/degree spatial frequency, 50 x 56 deg field size). Cone–driven ERGs in response to diffuse light flashes superimposed on a rod–adapting background (FERG) were also recorded.
PERG amplitudes decreased with increasing age (PERG amplitude (µV) = 9.26 –0.681 * Age (months); R2 = 0.26, P<0.001). The PERG amplitude of 12–14 month–old mice was close to that of noise (mean 1.5 µV). The amplitude ratio between PERG and FERG (P/F) also decreased with age (P/F = 0.216 –0.0125 * Age (months); R2 = 0.18, P<0.001). This indicates a predominant loss of inner retina function compared to outer retina with advancing age. PERG amplitudes were rather asymmetric between the two eyes (mean interocular difference = 41.1 ±38%). Interocular asymmetries in PERG amplitude did not correlate with corresponding asymmetries in FERG amplitude, indicating that inner retina changes were not secondary to outer retina changes.
The PERG is a useful technique to non– invasively measure age–related changes of inner retina activity in DBA/2J mice. With our optimized protocol the dynamic range of PERG amplitude is large enough to allow longitudinal studies aimed at monitoring progression of functional changes and determining functional endpoints. After one year of age the residual RGC function of DBA/2J mice appears to be very small on average. The large spread of amplitude values among mice of similar age, and the substantial interocular asymmetry in amplitude in individual mice are consistent with the reported large variability in disease development between mice and between eyes (John et al, IOVS, 1998, 39: 951).
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