Purchase this article with an account.
R. A. Jacoby, C. Cowan, M. Abd-El-Barr, S. Orengo-Nania, S. M. Wu, R. L. Gross; Retinal Ganglion Cells Display Lowered Sensitivity and Broadened Operating Range Upon Disease Onset in the Murine DBA2/J Glaucoma Model. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2775.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To characterize the temporal and spatial progression of retinal ganglion cell (RGC) dysfunction in the DBA2/J glaucomatous mouse model relative to RGC death, age, and intraocular pressure (IOP) increase.
Retinas from C57/Bl6 (WT) and DBA2/J mice aged between 6 and 25 months were placed on a multielectrode array (MEA) where RGCs responses were recorded during light steps of varying wavelength and intensity. Spike waveforms were extracted and principal components were used to identify single neural units across all intensities from each channel. Firing rates of each neural unit were plotted against stimulus intensity and fit to an intensity response (Michaelis-Menten) function. The intensity where firing rate was half maximal, a free parameter in the intensity response function, was used to assay sensitivity loss in the RGC population. The MEA was also used to record focal electroretinograms (ERG) from nearby tissue, providing insight into photoreceptor and bipolar cell function.
(1) By 6 months, DBA2/J mice showed a marked increase in low sensitivity RGC number compared to WT animals. Previous morphological studies in the DBA2/J animals have shown a rise in IOP, and associated RGC death, as early as 8 months. Consistent with this, no change in total visually responsive RGC number compared to WT was noted at 6 months. (2) 18 month old DBA2/J mice typically had lost all but patches of visually evoked RGC activity, despite retaining normal ERGs in the channels devoid of RGC responses. This RGC response loss is consistent with the RGC cell death beginning at 8 months, as noted above. The remaining patches of RGCs contained the same percentage of low sensitivity RGCs that was seen in the 6 month time point. (3) At 21 and 25 months the DBA2/J strain showed a near complete absence of RGC activity, yet retained strong ERGs on every channel. Collectively these results suggest that glaucomatous animals may exhibit RGC dysfunction manifested by a decrease in sensitivity.
Retinal ganglion cells in glaucomatous animals such as DBA/2J mice appear to exhibit sensitivity decline before substantial ganglion cell loss, suggesting that RGC sensitivity measurements may be used as a tool for early detection and treatment in glaucoma.
This PDF is available to Subscribers Only