l-DOPA stimulates the dopaminergic phenotype in human retina
Retinal organoids derived from inducible pluripotent stem cells were used to gain insight into the role of l-DOPA during human retinal development. Dopaminergic gene expression was indicated by assessing two dopamine receptors (DRD1 and DRD2), DOPA decarboxylase (DDC), and tyrosine hydroxylase (TH) via quantitative reverse transcription-polymerase chain reaction at various developmental stages. TH transcript levels started to express around day (D) 42, reached maximal expression [~]D63 and then decreased thereafter. At D29, proliferating retinal progenitors expressed DRD1, DRD2, and DDC at various levels of mRNA throughout the day. In the presence of l-DOPA, D29 retinal organoids expressed DRD1 but DRD2 mRNA expression was suppressed. Additionally, l-DOPA upregulated TH mRNA prior to dopaminergic amacrine cell (DAC) development. After the appearance of DACs, l-DOPA phase shifted expression of DRD2 and synchronized mRNA expression of DDC, DRD2, and TH. The present results suggest unique mechanisms for DA signaling at different stages of development in the human retina.