Adenosine as a signaling molecule in the retina: biochemical and developmental aspects

The nucleoside adenosine plays an important role as a neurotransmitter or neuromodulator in the central nervous system, including the retina. In the present paper we review compelling evidence showing that adenosine is a signaling molecule in the developing retina. In the chick retina, adenosine transporters are present since early stages of development before the appearance of adenosine A1 receptors modulating dopamine-dependent adenylate cyclase activity or A2 receptors that directly activate the enzyme. Experiments using retinal cell cultures revealed that adenosine is taken up by specific cell populations that when stimulated by depolarization or neurotransmitters such as dopamine or glutamate, release the nucleoside through calcium-dependent transporter-mediated mechanisms. The presence of adenosine in the extracellular medium and the long-term activation of adenosine receptors is able to regulate the survival of retinal neurons and blocks glutamate excitoxicity. Thus, adenosine besides working as a neurotransmitter or neuromodulator in the mature retina, is considered as an important signaling molecule during retinal development having important functions such as regulation of neuronal survival and differentiation

Development of nitric oxide synthase in the avian retina

Nitric oxide is an important intercellular messenger in the central nervous system. Our previous work showed the presence of NADPH-diaphorase activity, that partially corresponded to nitric oxide synthase, in the chick embryo retina. In the present study, we have demonstrated the presence of nitric oxide synthase in the chick retina measuring the conversion of 3(H)arginine to 3(H)citrulline. We found that the enzyme is dependent on the presence of calcium, calmodulin and NADPH and is inhibited by the arginine analog L-N(G) -nitroarginine. The enzyme activity was higher at 8-day-old embryonic retinas, decreased at 13-14 days and attained minimal levels at 15 days up to the post-hatching period. Glutamate stimulated nitric oxide synthase activity approximately 4 fold, an effect that was blocked by the NMDA antagonist MK-801. The results indicate that the glutamate/nitric oxide system has important fuctions during retinal development.