G‐protein‐coupled estrogen receptor protects retinal ganglion cells via inhibiting endoplasmic reticulum stress under hyperoxia

2020 ◽  
Author(s):  
Rong Li ◽  
Yao Wang ◽  
Pei Chen ◽  
Jiamin Meng ◽  
Hongbing Zhang
Keyword(s):  
Endoplasmic Reticulum ◽  
Estrogen Receptor ◽  
Endoplasmic Reticulum Stress ◽  
G Protein ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
G Protein Coupled

scholarly journals Molecular determinants of response kinetics of mouse M1 intrinsically-photosensitive retinal ganglion cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yanghui Sheng ◽  
Lujing Chen ◽  
Xiaozhi Ren ◽  
Zheng Jiang ◽  
King-Wai Yau
Keyword(s):  
G Protein ◽  
Retinal Ganglion Cells ◽  
Time Constant ◽  
Room Temperature ◽  
Time Course ◽  
Ganglion Cells ◽  
Functional Difference ◽  
Retinal Ganglion ◽  
Time Constants ◽  
Flash Response

AbstractIntrinsically-photosensitive retinal ganglion cells (ipRGCs) are non-rod/non-cone retinal photoreceptors expressing the visual pigment, melanopsin, to detect ambient irradiance for various non-image-forming visual functions. The M1-subtype, amongst the best studied, mediates primarily circadian photoentrainment and pupillary light reflex. Their intrinsic light responses are more prolonged than those of rods and cones even at the single-photon level, in accordance with the typically slower time course of non-image-forming vision. The short (OPN4S) and long (OPN4L) alternatively-spliced forms of melanopsin proteins are both present in M1-ipRGCs, but their functional difference is unclear. We have examined this point by genetically removing the Opn4 gene (Opn4−/−) in mouse and re-expressing either OPN4S or OPN4L singly in Opn4−/− mice by using adeno-associated virus, but found no obvious difference in their intrinsic dim-flash responses. Previous studies have indicated that two dominant slow steps in M1-ipRGC phototransduction dictate these cells’ intrinsic dim-flash-response kinetics, with time constants (τ1 and τ2) at room temperature of ~ 2 s and ~ 20 s, respectively. Here we found that melanopsin inactivation by phosphorylation or by β-arrestins may not be one of these two steps, because their genetic disruptions did not prolong the two time constants or affect the response waveform. Disruption of GAP (GTPase-Activating-Protein) activity on the effector enzyme, PLCβ4, in M1-ipRGC phototransduction to slow down G-protein deactivation also did not prolong the response decay, but caused its rising phase to become slightly sigmoidal by giving rise to a third time constant, τ3, of ~ 2 s (room temperature). This last observation suggests that GAP-mediated G-protein deactivation does partake in the flash-response termination, although normally with a time constant too short to be visible in the response waveform.

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