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M. Saleh, M. Nagaraju, V. Porciatti; The Natural History of Retinal Ganglion Cell Dysfunction and Its Relationship With IOP in DBA2/J Mice. Invest. Ophthalmol. Vis. Sci. 2007;48(13):210.
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To characterize the natural history of retinal ganglion cell (RGC) dysfunction, as measured by pattern electroretinogram (PERG) and its relationship with IOP in glaucomatous DBA/2J mice.
IOP and PERG were longitudinally recorded (one month steps) in anesthetized (Ketamine/ Xylazine) DBA 2/J mice (n=32, 64 eyes). IOP was measured with a rebound tonometer (Tonolab, Colonial Medical Supply). PERG was recorded in response to high contrast (95%) alternating (1 Hz) gratings (0.05 cycles/deg, 50 x 56 deg field size). Diffuse light flashes on an adapting background (FERG) were also recorded as an index of outer retina activity. After the follow up period, eyes were histologically processed to evaluate the thickness of the retinal nerve fiber layer (RNFL).
IOP increased moderately between 2 and 6 months with a progression of 0.92 mm Hg/month. After 6 months the IOP displayed a steeper increase and tended to level off by 11 months. The PERG amplitude decreased progressively after 2 months of age to reach the noise level (85% amplitude loss) at about 10-11 months, at which age histological analysis showed a relatively minor loss of retinal nerve fiber layer (RNFL) thickness (-39±18%). IOP and PERG changes with time were highly correlated (p<0.001). Between 2 and 11 months the cone-flash ERG did not show significant changes.
In DBA/2J mice inner retina function progressively decreases after 2 months of age and it is virtually abolished by 10-11 months, while outer retina function is unchanged. In keeping with previous optic nerve histology (Libby et al, Vis Neurosci 2005), at 10-11 months the RNFL thickness is relatively spared, thereby indicating that RGC dysfunction may precede RGC death. Progression of inner retina dysfunction is strongly associated with progressive IOP increase.
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