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Rachel Care, Ivan Anastassov, Felice Dunn; Compensation in the primary rod pathway following partial rod loss in the mature retina. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4785.
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© ARVO (1962-2015); The Authors (2016-present)
Understanding the function of the deafferented mature retinal circuit is critical for therapeutic efforts to rescue its function. Extensive work in models of rod degenerations has demonstrated the capacity of the developing retina to compensate for input loss, but little is known about whether this capacity extends beyond development. Here we induce partial rod death in mature retina and measure function throughout the rod pathway to identify potential sites of compensation.
We expressed the diphtheria toxin receptor (DTR) under the rhodopsin promoter (iRho-Cre) and partially ablated the rod population with diphtheria toxin injection at postnatal day 30 (Control: 7.3 ± 2.2; DTR: 4.5 ± 0.6 rows of rod cell bodies, p<0.005). To measure the functional output of the mature retina after partial rod loss, we made cell-attached and whole-cell patch-clamp recordings from alpha ON-sustained ganglion cells (AON-S GC) in ventral retina. We presented 10msec flashes of blue light or UV light on a blue mean to selectively stimulate either rods or cones, respectively. To understand the excitatory pathway leading to these ganglion cells, we made whole-cell voltage- and current-clamp recordings from rod bipolar cells in retinal slices.
After partial rod loss, the intensity response function of AON-S GC spiking showed increased sensitivity (Control: 9.03 ± 8.9, n=5; DTR: 2.7 ± 1.5 Rh*/rod, n=7; p=0.017). However, there was no change in the sensitivity of the excitatory currents onto these cells (Control: 6.42 ± 3.9, n=5; DTR: 5.74 ± 11.5 Rh*/rod, n=7; p=1). Similarly, whole-cell recordings in rod bipolar cells showed no difference in the sensitivity of the excitatory currents onto these cells after partial rod loss (Control: 4.36 ± 1.8, n=18; DTR: 4.81 ± 2.1 Rh*/rod, n=9; p=0.78).
These findings indicate that mature retina can compensate for partial rod loss. Our data suggest that one site of compensation is the current-to-spike generation within AON-S GCs. Because the sensitivity of their spiking response was greater than the sensitivity of the excitatory currents that drive this response, we conclude that these cells increase their excitability after partial rod loss. Our results also suggest that compensation occurs at the rod-to-rod bipolar synapse because at the level of excitatory currents onto rod bipolar cells, the circuit’s sensitivity has already recovered from partial rod loss.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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