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A. A. Thomas, R. D. Nobles, G. R. Howell, S. W. John, M. A. McCall; Changes in Retinal Ganglion Cell Spontaneous and Visually-Evoked Responses in the DBA2J Mouse Model of Glaucoma. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5794.
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© ARVO (1962-2015); The Authors (2016-present)
Glaucoma is a blinding eye disease frequently associated with increased intraocular pressure (IOP) and slow deterioration of retinal ganglion cell (RGC) dendrites and axons. DBA/2J mice show age-related hallmarks of human glaucoma: IOP elevation, optic nerve cupping and RGC death. We recorded spontaneous and visually-evoked RGC responses in the optic nerve of DBA/2J and control mice to catalogue age-related changes.
Responses were recorded from RGCs in DBA/2J and control DBA/2J-Gpnmb+ that do not develop high IOP. RGC responses were recorded extracellularly in an in vivo preparation at 3, 5-7, or 10-12 months of age. Responses were evoked by 1Hz drifting gratings at contrasts from 10 - 100% and spatial frequencies from 0.01 - 0.26 c/d. Receptive field size and surround antagonism also were evaluated. A Fast Fourier Transform algorithm determined the fundamental component of each response to drifting gratings. DBA/2J and DBA/2J-Gpnmb+ and C57bl/6J (WT) response properties were compared using ANOVAs.
While DBA/2J-Gpnmb+ and WT RGC responses are similar at 3 and 5-7 months, DBA/2J RGCs show significant loss in visual responses to drifting gratings. Both high spatial resolution and response amplitude are lower in DBA/2J RGCs than controls. The spontaneous activity (SA) of DBA/2J RGCs was significantly reduced beginning at 5-7 months and ON-center RGCs were more affected than OFF-center RGCs. At 10 - 12 months of age, there were significantly fewer DBA/2J RGCs with either SA and/or visually-evoked activity.
We found that visual function of DBA/2J RGCs declines with age. Both SA and visually-evoked responses of RGCs are reduced, suggesting that their inputs or post-synaptic receptors are negatively affected. The greater effect on the SA of ON-center RGCs supports the presynaptic input hypothesis; ON-center RGC SA depends on excitatory input, whereas Off-center RGC SA is intrinsically generated (Margolis & Detwiler, 2007). These changes also are consistent with observed changes in RGC dendritic arbors in this mouse model (Jakobs & Masland, 2005). The decrease in RGC responses to high spatial frequencies as well as the reduction in the numbers of responsive RGCs with age is consistent with changes reported in the visual capacity of glaucoma patients. Taken together, the DBA/2J mouse represents a good model of the human glaucomatous retina and should become increasingly useful for explorations of therapeutic agents.
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