TRAFFICKING OF MOLECULES AND METABOLIC SIGNALS IN THE RETINA

Photoreceptors need the support of pigment epithelial (PE) and Muller glial cells in order to maintain visual sensitivity and neurotransmitt er resynthesis. In rod outer segments (ROS), all-trans-retinal is tran sformed to all-trans-retinol by retinol dehydrogenase using NADPH. NAD PH is restored in ROS by the pentose phosphate pathway utilizing high amounts of glucose supplied by choriocapillaries. The retinal formed i s transported to PE cells where regeneration of Il-cis-retinal occurs. Muller cells take up and metabolize glucose predominantly to lactate which is massively released into the extracellular space (ES). Lactate is taken up by photoreceptors, where it is transformed to pyruvate wh ich, in turn, enters the Krebs cycle in mitochondria of the inner segm ent. Stimulation of neurotransmitter release by darkness induces 130% rise in the amount of glutamate released into ES. Glutamate is transpo rted into Muller cells where it is predominantly transformed to glutam ine. Stimulation of photoreceptors induces an eightfold increase in gl utamine formation. It appears, therefore, that there is a signaling fu nction in the transfer of amino acids from Muller cells to photorecept ors. Work on the model-system of the honeybee retina demonstrated that photoreceptors release NH4+ and glutamate in a stimulus-dependent man ner which, in turn, contribute to the biosynthesis of alanine in glia. Alanine released into the extracellular space is taken up and used by photoreceptors. Glial cells take glutamate by high-affinity transport ers. This uptake induces a transient change in glial cell metabolism. The transformation of glutamate to glutamine is possibly also controll ed by the uptake of NH4+ which directly affects cellular metabolism. ( C) 1998 Elsevier Science Ltd. All rights reserved.