l-Arginine Uptake in Normal and Diabetic Rat Retina and Retinal Pigment Epithelium

Abstract

Diabetes-induced increase in oxidative stress is postulated as playing a significant role in the development of retinopathy. The retinal pigment epithelium (RPE) which forms part of the retinal blood barrier has been reported to be affected in diabetes. Besides functioning as a neurotransmitter, the radical nitric oxide (NO) can act as a cytotoxic agent. NO is synthesized by nitric oxide synthase (NOS) that oxidizes arginine to citrulline producing NO. Given that intracellular concentration of arginine depends mainly on its transport, we studied arginine transport in RPE and retina from normal and streptozotocin-induced diabetic rats. Retina and RPE take up arginine by a saturable system with an apparent K(M) of 70-80 microM. Tissue incubation in the presence of insulin or high glucose concentrations significantly increased arginine transport in RPE but not in retina from control rats. Similarly, arginine uptake was enhanced in RPE, but not in the retina from streptozotocin-induced diabetic rats. However, NO content was two-fold higher in diabetic retina and RPE compared to that in the control rats. Such findings may suggest that diabetes induced an increase in NO levels in RPE, which may have brought about alterations in its functioning and in turn manifestations of diabetic retinopathy.

Supplementation with apple enriched with L‐arginine may improve metabolic control and survival rate in alloxan‐induced diabetic rats

“…In this experimental condition, our results suggest that diabetes (or high glucose levels in cells derived form normoglycemic animals) exhibit a reduced L-arginine uptake, probably via CAT-1 and/or CAT-2B. In this regard, our results differ from previous studies where high glucose exposition was associated to an increased L-arginine transport in human umbilical vein endothelial cells (HUVEC) [34,35] or in retinal pigment epithelium [36]. Differences are attributed to cell type, as well as experimental conditions, since longer (hours) rather than rapid (minutes) exposition was used in our study.…”

Nitric oxide leads to cytoskeletal reorganization in the retinal pigment epithelium under oxidative stress

“…Our results demonstrate that oxidative stress induced disassembly of vimentin intermediate filaments may cause vimentin phosphorylation in the RPE. L-Arginine uptake by RPE cells significantly increases the NO levels in diabetic rat RPE [40]. The current study implies dual roles of NO that 1 - 10 nmole·cm −2 ·min −1 of NO may protect RPE cell by PP2A and vimentin phosphorylation, whereas higher NO (>100 nmole·cm −2 ·min −1 ) generation under oxidative stress may induce apoptosis.…”

Plasma levels of amino acids and derivatives in retinopathy of prematurity

“…A recent study indicated that long-term use of L-citrulline is effective in the prevention of retinal vascular dysfunction induced by diabetes mellitus, and it may have a potential prophylactic effect in DR 21 . Nitric oxide synthase (NOS) could oxidize arginine to citrulline and induce the production of nitric oxide (NO), and diabetes upregulated NO levels in retinal pigment epithelium (RPE), indicating that NO may alter the function of RPE leading to DR pathogenesis 22 . As a regulating enzyme of arginine metabolism, arginase 2 participates in neurodegeneration during ROP pathogenesis, and deficiency of arginase 2 ameliorates the survival and function of neurons and reduces retinal neurodegeneration in vivo 23 , 24 .…”