Abstract
Purpose :
Vertebrate color vision requires the differential expression of specific cone opsins in separate cone populations. One model for the regulation of the human long and medium wavelength sensitive (LWS/MWS) opsin tandem array suggests an upstream regulatory region interacts with replicated opsin genes at random, resulting in mutually exclusive expression of a specific opsin. However, our prior investigations into the orthologous long wavelength sensitive (lws1/lws2) array in zebrafish suggest that thyroid hormone (TH) and retinoic acid serve as trans regulators of this gene array in larvae/juveniles (Mitchell et al., 2015, PLOS Genetics; Mackin et al., 2019, PNAS). This study investigates whether cone opsin expression remains plastic to TH treatment in adult zebrafish, where cone distribution is considered stable.
Methods :
Adult zebrafish (both sexes) were treated with NaOH (0.01%, control) or TH (386 nM) for 1 or 5 days (n=3). Left eyes were harvested for qPCR analysis and right eyes for cryosectioning. A set of lws reporter transgenic adults (lws:PAC(H); lws1 reported by GFP and lws2 reported by RFP) were also treated for 5 days with NAOH or TH (n=3). Whole retinas and cryosections were analyzed by confocal imaging.
Results :
In adult zebrafish, exogenous TH drastically increased lws1 expression in both 1 and 5 day-treated groups (p=0.003, 0.0006, respectively) while decreasing lws2 expression (p=0.002, 0.005). Other phototransduction-related transcripts that were shown to decrease in embryos and juveniles exposed to TH showed a similar response in adults: gngt2b (p=0.09, 0.003), rh2-1 (p=0.05, 5 day treatment). TH treated transgenic lws reporter line revealed a clear switch from lws2 to lws1 in dorsal retina, consistent with the qPCR data. Whole retinas of transgenic reporters demonstrate an expansion of lws1-expressing cones nasally and dorsally as well.
Conclusions :
Exogenous TH induced a drastic shift from lws2 to lws1 in adult zebrafish, consistent with previous studies of larvae and juveniles. This shift occurs as rapidly as 1 day when exposed to TH, which shows that cones remain highly plastic even into adulthood. Plasticity in spectral sensitivity (to be sensitive to higher wavelengths) in response to TH suggests a role in visual system function well into adulthood.
This is a 2021 ARVO Annual Meeting abstract.