Abstract
Purpose :
During the early stages of retinal degeneration rod photoreceptors begin to functionally uncouple from downstream rod bipolar cells, retracting their synaptic terminals. Previous studies have shown that rod bipolar cells lack a light-evoked response under these conditions even though some synaptic puncta remain at their dendritic tips. We tested whether the lack of rod bipolar response is due to impaired glutamate release from rods, or deficient mGluR6 transduction in bipolar dendrites.
Methods :
Voltage clamp recordings from rod bipolar cells were made with patch electrodes in dark-adapted retinal slices from 1- and 2-month-old CNGB1neo/neo mice, which display gradual retinal degeneration over 6 months. Light responses were evoked by an LED (λmax ~ 405nm). Responses in the absence of light were evoked with puffs of the weak mGluR6 antagonist, CPPG, onto their dendrites while the retina was bathed in Ames’ media with and without the strong mGluR6 agonist, DL-AP4.
Results :
Light-evoked responses in 1- and 2-month-old CNGB1neo/neo rod bipolar cells were largely absent, consistent with previous studies. In these same bipolar cells, puffs of the glutamate receptor antagonist CPPG (1 mM) also evoked either a minimal or no inward current. The size of the inward current increased in some rod bipolar cells when the solution bathing the retina also contained 5 mM DL-AP4. Puffs of CPPG in control retinas produced an inward current, which was also increased in the presence of DL-AP4.
Conclusions :
Rod bipolar cells largely lack light-evoked responses in the degenerating retina, and under these conditions support minimal responses to puffs of CPPG. The increased response size to CPPG in the presence of DL-AP4 suggests that the molecular machinery remains in place to support responses, but that reduced rod glutamate release causes this mGluR6 machinery to be strongly desensitized. The retained ability of mGluR6 transduction to open TRPM1 channel during degeneration may explain why rod-to-rod bipolar cell synapses can be strengthened following the rescue of rod function.
This is a 2021 ARVO Annual Meeting abstract.