l‐DOPA supply to the neuro retina activates dopaminergic communication at the early stages of embryonic development

Abstract

DOPA decarboxylase (DDC; aromatic-L-amino acid decarboxylase; EC 4.1.1.28) is absent in retinas from 6-day-old chicken embryos (E6) but is expressed in retina of E8 embryos, in the presumptive outer plexiform layer. Thereafter, DDC appears in cell bodies of presumptive amacrine cells. The dopamine (DA) content of E9/10 and E15/16 retinas, preincubated with L-DOPA for 1 h, increased 250-and 600-fold, respectively, showing that DDC is active since early in development. Intercellular communication, measured by endogenous cyclic AMP accumulation, was observed when retinas from E9/10 to E15/16 were pre-incubated for 1 h with 1 mM L-DOPA, washed and followed by incubation in the presence of 0.5 mM 3-isobutyl-1-methylxanthine, a phosphodiesterase inhibitor. Cyclic AMP accumulation was prevented when pre-incubation with L-DOPA was carried out in the presence of carbidopa. Moreover, the accumulation of cyclic AMP was inhibited by SCH 23390 (2 lM). The incubation of retinas in medium previously conditioned by retinapigmented epithelium (RPE) also increased its cyclic AMP content with the characteristics described for L-DOPA. Our results show that dopaminergic communication takes place in the embryonic retina, before tyrosine hydroxylase expression, provided L-DOPA is supplied to the tissue. It also shows that RPE is a potential source of L-DOPA early in development.

Müller Glia as an Active Compartment Modulating Nervous Activity in the Vertebrate Retina: Neurotransmitters and Trophic Factors

“…Also, D 2 dopaminergic receptors were found in isolated rat and guinea-pig Müller cells [107]. DDC, in particular, is expressed in the embryonic avian retina as early as embryonic day 8, prior to the expression of TH [106]. In this tissue, DDC immunolocalization revealed that the enzyme is detected in the presumptive outer plexiform layer, suggesting that part of this enzyme could be located in the Müller cells endfeet.…”

“…D 1 receptor, Tyrosine Hydroxylase (TH), L-Dopa-Decarboxilase (DDC) and the dopamine transporter DAT are expressed by cultured Müller cells [41,106]. Also, D 2 dopaminergic receptors were found in isolated rat and guinea-pig Müller cells [107].…”

“…In this tissue, DDC immunolocalization revealed that the enzyme is detected in the presumptive outer plexiform layer, suggesting that part of this enzyme could be located in the Müller cells endfeet. Moreover, DDC in early embryonic avian retina is capable of converting L-DOPA into dopamine (DA) and activate dopaminergic activity in the tissue before TH is expressed [106,108]. This is accomplished because retinal pigmented epithelium supplies the neuro-retina with L-Dopa synthesized by tyrosinase [106].…”

Intrastriatal Transplantation of Retinal Pigment Epithelial Cells for the Treatment of Parkinson Disease: In Vivo Longitudinal Molecular Imaging with18F-P3BZA PET/CT

“…Apart from L-DO-PA production, human RPE (hRPE) cells can also produce a small amount of dopamine directly and possess other molecular machinery involved in dopamine production and regulation (7)(8)(9)(10). Therefore, hRPE cells attached to gelatin microcarriers have been explored as a promising source of donor cells for neural transplantation in the treatment of Parkinson disease by providing "L-DOPA pumps" to maintain stable L-DOPA levels (11).…”

Tyrosinase Is the Modifier of Retinoschisis in Mice

“…It has been postulated that the middle product, L-dopa, is released from RPE cells into the extracellular space (Page-McCaw et al 2004). L-dopa is known to affect retinal development and function (Kubrusly et al 2003;Tibber et al 2006), and it is also the precursor of dopamine, a neurotransmitter produced by dopaminergic neurons that has roles in retinal development and function as well (Reis et al 2007). Thus, the Tyr mutation may decrease the concentration of L-dopa and dopamine in the retina, which may in turn affect Rs1 mutant phenotypes in the retina.…”