Abstract
Purpose :
In the retina, serotonin is implicated in neural processing, visual acuity, and neural development. There is some evidence that Selective Serotonin Reuptake Inhibitors (SSRIs), which increase the availability of extracellular serotonin, have a protective association against retinal neurodegenerative diseases such as glaucoma. Despite this potential importance, little is known about the mechanisms by which serotonin functions in the retina. For example, serotonin acts through serotonin receptors (HTRs), but little is known about the cellular distribution of HTRs in the adult retina. As glaucoma is a disease of retinal ganglion cells (RGCs), the purpose of this study is to investigate the expression and function of serotonin receptors in RGCs.
Methods :
Adult mouse RGCs were isolated via immunopanning and underwent RNA sequencing as part of a previous study (Park et al., 2019). Sequence data were re-analyzed to determine the relative expression level of all known Htr genes. Immunohistochemistry (IHC) was performed in mouse retinal whole-mounts and 50 µm sections using primary antibodies to HTR1B and HTR1D, and imaged using confocal microscopy. Visual behavior was determined in Htr1b knockout (KO) mice using contrast-dependent optokinetic responses (OKRs) under scotopic and photopic conditions.
Results :
Twelve Htr genes were expressed in adult RGCs, with Htr1b and Htr1d at the highest levels. IHC confirmed that HTR1B protein was present diffusely throughout the ganglion cell layer and inner plexiform layer, and that HTR1D protein was present in the ganglion cell layer where it labeled some but not all RGCs. Preliminary OKR analysis of 8-week old Htr1b KO mice (N = 6 eyes) showed reduced scotopic contrast sensitivity compared to heterozygous littermate controls (N = 18 eyes). However, contrast sensitivity did not vary significantly between groups at 20 weeks of age.
Conclusions :
HTR1B and HTR1D are both expressed in RGCs, with HTR1B showing a broader pattern. Furthermore, our results suggest that HTR1B may be required for normal scotopic visual function in young adults but not older adults and therefore play a transient role in vision. Further studies will confirm these results and investigate additional roles of key serotonin receptors in RGC biology.
This is a 2021 ARVO Annual Meeting abstract.