Purpose: To clarify the functions of a specific subtype of thyroid hormone receptor (TR), TRbeta2, and photoreceptor cell-specific nuclear receptor (PNR) in the development of cone photoreceptors.
Methods: The expression of short (S)- and medium (M)-wavelength cone opsins was analyzed by reverse transcription polymerase chain reaction (RT-PCR) and Northern blot analysis in mice without a functional PNR (rd7/rd7 mice), and levels of plasma thyroid hormones and expression of TRbeta2 were also examined. Concomitantly, by means of reporter assays, the roles of PNR and TRbeta2 in the S- and M-cone opsin expression were explored at the transcriptional level.
Results: In rd7/rd7 mice, an abnormal increase in cone photoreceptors was observed immediately before retinal maturation normally occurs. Although an increase in S-cone opsin in the retina was observed during and after retinal development, the expression of M-cone opsin expression was not perturbed during retinal maturation. Plasma concentrations of thyroid hormone and levels of TRbeta2 expression in the rd7/rd7 mouse retina over the developmental period were normal. Transcriptional studies demonstrated that TRbeta2, but not PNR, activated the M-cone opsin gene promoter function, while suppressing the S-cone opsin promoter function enhanced by CRX in a thyroid hormone-dependent manner.
Conclusions: The results indicate that PNR may suppress proliferation of cone photoreceptor progenitor cells and that the regulation of S- and M-cone opsin gene expression is mediated by TRbeta2 and CRX, but not by PNR. Thus, our results partly disclosed the molecular mechanism of cone photoreceptor development, highlighting the distinct functions of PNR and TRbeta2.