Retinol-binding protein 4 (RBP4) is the sole specific transport protein for vitamin A (retinol), but it is also an adipokine with retinol-independent, proinflammatory activity associated with diabetes and diabetic retinopathy (DR). Most previous studies focused on the relationship between elevated serum RBP4 levels and DR. Since serum RBP4 cannot cross the blood-retinal barrier, the level of retinal RBP4 is independent of serum RBP4, and the change of retinal RBP4 and its potential pathogenic mechanism in DR has not been studied. We showed that the retinal RBP4 levels were raised in Streptozotocin-induced diabetic mice though the serum RBP4 levels were decreased. Intravitreal injection of RBP4 protein in mice results in activation of microglia, loss of retinal ganglion cells (RGCs) and bipolar cells. Minocycline (MC) can reverse the activation of microglia induced by RBP4, protecting RGCs and bipolar cells. These findings suggest that retinal RBP4 levels were raised in diabetic mice, and RBP4 can directly induce retinal neurodegeneration in mice through microglia. RESEARCH HIGHLIGHTS: We revealed that the retinal RBP4 levels were raised in diabetes and elevated retinal RBP4 can induce retinal neurodegeneration through microglia. Inhibition of neuroinflammation or reduction of retinal RBP4 level may be a potential therapeutic strategy to prevent diabetic retinal neurodegeration.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1002/jemt.24258 | DOI Listing |
J Vis Exp
October 2024
Department of Ophthalmology and Visual Neurosciences, University of Minnesota;
Distribution of dietary vitamin A/all-trans retinol (ROL) throughout the body is critical for maintaining retinoid function in peripheral tissues and generating the retinylidene protein for visual function. RBP4-ROL is the complex of ROL with retinol-binding protein 4 (RBP4), which is present in the blood. Two membrane receptors, Retinol Binding Protein 4 Receptor 2 (RBPR2) in the liver and STimulated by Retinoic Acid 6 Retinol (STRA6) in the eye, bind circulatory RBP4 and this mechanism is critical for internalizing ROL into cells.
View Article and Find Full Text PDFInt J Mol Sci
April 2024
Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN 55455, USA.
In this review, we outline our current understanding of the mechanisms involved in the absorption, storage, and transport of dietary vitamin A to the eye, and the trafficking of rhodopsin protein to the photoreceptor outer segments, which encompasses the logistical backbone required for photoreceptor cell function. Two key mechanisms of this process are emphasized in this manuscript: ocular and systemic vitamin A membrane transporters, and rhodopsin transporters. Understanding the complementary mechanisms responsible for the generation and proper transport of the retinylidene protein to the photoreceptor outer segment will eventually shed light on the importance of genes encoded by these proteins, and their relationship on normal visual function and in the pathophysiology of retinal degenerative diseases.
View Article and Find Full Text PDFPLoS One
October 2023
Swiss Eye Institute, Rotkreuz, and Berner Augenklinik, Bern, Switzerland.
Diabetic retinopathy (DR) is a frequent microvascular complication of diabetes mellitus, and inflammatory pathways have been linked to its pathogenesis. In this retrospective, observational pilot study, we aimed to compare the concentrations of four inflammation-related proteins, ZAG, Reg-3a, elafin and RBP-4, in the serum and aqueous humor of healthy controls and diabetic patients with different stages of DR. The concentrations of VEGF-A, IL-8, IL-6 were determined in parallel as internal controls.
View Article and Find Full Text PDFJ Med Genet
December 2023
Laboratoire National de Référence (LBMR), Génétique des anomalies malformatives de l'œil, CHU Toulouse, Toulouse, France.
Background: The retinoic acid (RA) pathway plays a crucial role in both eye morphogenesis and the visual cycle. Individuals with monoallelic and biallelic pathogenic variants in (), encoding a serum retinol-specific transporter, display variable ocular phenotypes. Although few families have been reported worldwide, recessive inherited variants appear to be associated with retinal degeneration, while individuals with dominantly inherited variants manifest ocular development anomalies, mainly microphthalmia, anophthalmia and coloboma (MAC).
View Article and Find Full Text PDFDiagnostics (Basel)
July 2023
Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou Main Branch, Taoyuan 33305, Taiwan.
Age-related macular degeneration (AMD) may be associated with variants and is characterized by the accumulation of visual cycle-byproduct lipofuscin. Reducing retinol-binding protein 4 (RBP4), a retinol transporter protein, may reduce lipofuscin production. This study aims to assess the associations between plasma RBP4, the variation, and AMD severity.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!