Prolonged light adaptation reduces the expression levels of RGS proteins at the dendritic tips of rod bipolar cells

Abstract

Purpose : The mammalian visual system functions over a range of light intensities several orders of magnitudes apart. Vision in this large dynamic range is enabled by numerous adaptation mechanisms at different time scales in every step of retinal processing. Long-term adaptation (over a span of hours) has been studied in photoreceptors and ganglion cells, but little is known about this long-term adaptation in bipolar cells. Here we studied the effect of prolonged light adaptation on the expression level of the Regulators of G-protein Signaling (RGS) proteins that are essential for the light sensitivity of the rod bipolar cells.

Methods : To determine if such adaptation alters expression of RGS proteins, we immunostained dark- and light-adapted retinas, and then quantified and compared the protein levels in rod bipolar dendritic tips. To determine the electrophysiological effect of light adaptation in rod bipolar cells, we performed electroretinograms (ERG) in live mice adapted for at least 3 hours either in dark or to average “cage light” (around 30 lux). We then estimated rod bipolar cells’ response sensitivity as the ratio of the a-wave sensitivity to that of the b-wave sensitivity.

Results : Analyzing the ERG, we found that after light adaptation, the rod bipolar cells’ sensitivity decreased to 20 percent of dark adapted cells. Immunostaining for RGS7 and RGS11 showed that punctate staining of rod bipolar dendritic tips in light adapted retinas was 30 to 40 percent less than in dark-adapted retinas. To determine if the reduced staining in the dendritic tips involves protein degradation, we tested a mouse model lacking Ate1 (arginyltransferase 1, an enzyme that is required for ubiquitin-dependent degradation of RGS7 in neurons), and found no significant difference of RGS7 levels between light- and dark-adapted retinas of the knockout mice.

Conclusions : In rod bipolar cells, the decrease of RGS proteins is correlated with a decrease in response sensitivity after prolonged light adaptation, and it likely represents a mechanism for long-term gain control of the G-protein signaling. We suggest that under light adaptation, at least part of the decrease of RGS proteins is due to degradation, while under dark adaptation, RGS proteins are stabilized by the elevated rate of G-protein activation.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.