In the pig eye, oxygen and glucose consumption in the outer retina are reduced in light compared to the consumption in the dark and most of the glucose consumed is metabolized to lactate both in light and in the dark. In the present study, in order to characterize the metabolism of glucose in the inner retina. Blood was collected from an artery and from a plexus on the optic nerve draining blood from the retina. Arteriovenous concentration differences for glucose, lactate and oxygen were determined. Observations were made in dark-adapted eyes and then after light adaptation. The consumption of oxygen and glucose and the lactate formation in the inner retina were calculated on the basis of these observations and recent data for retinal blood flow. In dark-adapted eyes, approx. 69% of the glucose was oxidized and approx. 20% was used in lactate formation. After 5-10 min of exposure to constant light, the levels of oxygen consumption and lactate formation were no different from those in darkness. The results indicate that lactate formation is a normal property of the pig inner retina, but that it is much less pronounced than in the outer part. The metabolism of the inner retina in constant light is similar to that in darkness. A comparison with data for the outer retina indicates that oxygen consumption in the inner retina in constant light is approx. 47% of that in the whole retina, while for glucose consumption and lactate production, the corresponding figures are approx. 12 and 8%, respectively.

In the pig eye, oxygen and glucose consumption in the outer retina are reduced in light compared to the consumption in the dark and most of the glucose consumed is metabolized to lactate both in light and in the dark. In the present study, in order to characterize the metabolism of glucose in the inner retina. Blood was collected from an artery and from a plexus on the optic nerve draining blood from the retina. Arteriovenous concentration differences for glucose, lactate and oxygen were determined. Observations were made in dark-adapted eyes and then after light adaptation. The consumption of oxygen and glucose and the lactate formation in the inner retina were calculated on the basis of these observations and recent data for retinal blood flow. In dark-adapted eyes, approx. 69% of the glucose was oxidized and approx. 20% was used in lactate formation. After 5-10 min of exposure to constant light, the levels of oxygen consumption and lactate formation were no different from those in darkness. The results indicate that lactate formation is a normal property of the pig inner retina, but that it is much less pronounced than in the outer part. The metabolism of the inner retina in constant light is similar to that in darkness. A comparison with data for the outer retina indicates that oxygen consumption in the inner retina in constant light is approx. 47% of that in the whole retina, while for glucose consumption and lactate production, the corresponding figures are approx. 12 and 8%, respectively.

SummaryThis paper reviews quantitative studies on the permeability of retinal and choroidal vessels and the exchange of nutrients over the blood retinal barrier (BRB). The fen estrated capillaries in the choroid are very permeable to low molecular weight sub stances; sodium permeability in the choroid is probably SO times that in skeletal muscle. This results in high concentrations and rapid turnover of nutrients in the extra-vascular compartment of the choroid. Free diffusion is restricted by the pig ment epithelium barrier. Also the retinal capillaries, with tight junctions between the endothelial cells, have very low permeability even to sodium. The uptake index technique has provided evidence for several carrier systems in the BRB; hexoses, neutral and basic amino acids, and monocarboxylic acids, very similar to those found in the brain. At least for glucose and lactate these carriers operate at both levels of the BRB; the RPE and the endothelium of the retinal capillaries, and in both directions; i.e. inwards and outwards.The blood-retinal (BRB) and the blood-brain (BRB) barriers are physical hindrances for diffusion between blood and nervous tissue. They are essential for the control of the micro environment of the tissues:* by preventing noxious water-soluble mol ecules from entering the extravascular spaces of the retina and the brain. * by preventing uncontrolled escape of important ions from nervous tissue. Due to these barriers there is a need for specific carrier-mediated mechanisms for the exchange of nutrients and metabolites through the cells.Sinc� the retina in man and several other species has a dual vascular supply, the retinal and the choroidal vessels, the BRB has two parts, the endothelial cells of the retinal capil lary walls and the retinal pigment, epithelium (RPE). The barrier function depends on tight junctions which restrict intercellular move ment of all water-soluble molecules and thus virtually prevent these molecules from enter ing retinal tissue between the cells. 1 In clinical studies the integrity of the BRB can be eval uated by fluorescein angiography and vitreous fluorophotometry. These methods which pro vide qualitative, morphological and quantita tive information on the permeability of the BRB have increased our understanding of the pathogenesis of many retinal diseases.The aim of the present paper is to summar ise some quantitative experimental studies, performed in our laboratory, on the perme ability of the retinal and choroidal vessels and on the exchange of nutrients over the BRB.

The glucose metabolism of the retina was studied in vivo, by determining glucose, oxygen and lactate a-v differences for choroidal and retinal blood in pigs at different levels of intraocular pressure. At normal intraocular pressure the choroidal a-v differences were 0.07 and 0.11 mmol/l for glucose and oxygen respectively. The corresponding figures for the retina were 0.44 and 2.15. At increased levels of intraocular pressure the choroidal and retinal glucose and choroidal oxygen a-v differences increased, thus at least partly compensating for reduced blood flow. A major part of the oxygen and glucose consumed by the retina was delivered by the choroid. The total amount of oxygen extracted from choroidal and retinal blood could only account for complete oxidation of 37% of the extracted glucose. The results obtained in determinations of lactate a-v differences indicate that part of the remaining glucose is used for anaerobic glycolysis.

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The uptake-index method was used to study the transport of amino acids through the blood-retinal and blood-brain barriers in rats. The results indicate the existence of at least two different, similar carriers in both barriers, i.e., one each for neutral and basic amino acids. A third separate transport system for taurine was found in the blood-retinal barrier. All of the carrier systems studied transported amino acids from blood to nervous tissue.

The validity of the uptake index method for studies on passage through the blood-retinal barrier was evaluated. Data for the brain were also obtained for comparison. A rapid intracarotid injection of 0.2 ml buffered Ringer solution in rats did not result in a measurable increase in the permeability to EDTA for either the blood-retinal or the blood-brain barriers, while a markedly hypertonic solution caused an immediate osmotic breakdown of both barriers. For determinations of the retinal uptake index (RUI) 3HOH was found to be a suitable reference substance. A more diffusible reference, such as 14C-ethanol, resulted in a lower net extraction, probably due to a more rapid wash-out by the choroidal blood flow. Clearance of both reference and test substances from the retina was considerably faster than from the brain. For this reason a 5-s interval between the intracarotid injection and the enucleation was used as routine for determinations of RUI. With this technique RUI for the transported monosaccharide 3-O-methyl-D-glucose was significantly larger than for L-glucose, 53.8 and 14.2% respectively. The RUI for L-glucose was mainly due to L-glucose confined to extravascular choroidal fluid adhering to the retinal tissue samples. By prolonging the interval between injection and enucleation, and subtracting the activity due to recirculation, this extraretinal contamination could be practically eliminated. It is concluded that the uptake index method can be a useful tool in studies on transport of metabolic substrates through the blood-retinal barrier.

The retinal and brain uptake index method was utilized in a study on rats to evaluate the existence of transport systems for lactate in the blood-retinal and the blood-brain barrier, respectively. For both retina and brain a saturable, pH-dependent uptake of L-lactate was observed. The uptake could also be inhibited by pyruvate and 3-hydroxybuty-rate. It is concluded that lactate is transported through the blood-retinal and the blood-brain barriers by similar carrier-mediated transport systems with affinity also to other monocarboxylic acids, such as pyruvate, and to the ketone body 3-hydroxybutyrate. The pH-dependence of the lactate transport suggests that co-transport of H⁺ ions or counter-transport of OH^- ions takes place.