Elevation in Circulating Soluble CD40 Ligand Concentrations in Type 2 Diabetic Retinopathy and Association with its Severity

Lamine, Laila Ben; Turki, Amira; Al-Khateeb, Ghada; Sellami, N.; Amor, Hagger B.; Sarray, Sameh; Jailani, Mohamed; Ghorbel, Mohamed; Mahjoub, Touhami; Almawi, Wassim Y.

doi:10.1055/a-0647-6860

Cited by 16 publications

(17 citation statements)

References 37 publications

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“…CD40 expression level is low at basal condition, and its upregulation results in downstream inflammatory response in diseases (173). Plasma-soluble CD40 ligand level is found to be positively associated with DR severity (173). Increased expression of CD40 was found in retinal Müller cells, ECs, and microglial cells of diabetic animals (174).…”

Section: Cd40mentioning

confidence: 99%

“…CD40, a member of the TNF receptor superfamily, is expressed not only on monocytes, dendritic cells, and ECs but also on Müller glia, microglial cells, and retinal pigment epithelial cells (169,170). CD40 expression level is low at basal condition, and its upregulation results in downstream inflammatory response in diseases (173). Plasma-soluble CD40 ligand level is found to be positively associated with DR severity (173).…”

Section: Cd40mentioning

confidence: 99%

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Endothelial Dysfunction in Diabetic Retinopathy

Gui

You

et al. 2020

Front. Endocrinol.

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Diabetic retinopathy (DR) is a diabetic complication which affects retinal function and results in severe loss of vision and relevant retinal diseases. Retinal vascular dysfunction caused by multifactors, such as advanced glycosylation end products and receptors, pro-inflammatory cytokines and chemokines, proliferator-activated receptor-γ disruption, growth factors, oxidative stress, and microRNA. These factors promote retinal endothelial dysfunction, which results in the development of DR. In this review, we summarize the contributors in the pathophysiology of DR for a better understanding of the molecular and cellular mechanism in the development of DR with a special emphasis on retinal endothelial dysfunction.

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Section: Cd40mentioning

confidence: 99%

Section: Cd40mentioning

confidence: 99%

Endothelial Dysfunction in Diabetic Retinopathy

Gui

You

et al. 2020

Front. Endocrinol.

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“…These results were concordant with previous publications. 38,39 Microalbuminuria is the principal clinical phenotype of diabetic nephropathy. [40][41][42] Thus, higher levels of sCD40L in first years of diabetes could help as a prognostic indicator for predicting upcoming vascular complication in the future.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of soluble CD40L in children with type 1 diabetes mellitus and its relation to diabetes associated vasculopathy

Hodeib

Meabed

Abougabal

et al. 2021

Egypt J Pediatr Allergy Immunol

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“…Activation of CD40 on retinal Müller glia depends upon the presence of its ligand CD154. CD154 concentrations are enhanced in the blood of both diabetic patients and rodents, and plasma levels of soluble CD154 are positively correlated with the severity of DR (45,46). It remains unclear how CD154 gets into the retina prior to the development of inflammation; however, it is possible that microthrombosis in the retinal capillaries of patients with DR enables activation of platelets in the retina (47).…”

Section: Discussionmentioning

confidence: 99%

Diabetes enhances translation of Cd40 mRNA in murine retinal Müller glia via a 4E-BP1/2–dependent mechanism

Dierschke

Toro

Miller

et al. 2020

Journal of Biological Chemistry

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Activation of the immune costimulatory molecule cluster of differentiation 40 (CD40) in Müller glia has been implicated in the initiation of diabetes-induced retinal inflammation. Results from previous studies support that CD40 protein expression is elevated in Müller glia of diabetic mice; yet, the mechanisms responsible for this increase have not been explored. Here, we evaluated the hypothesis that diabetes augments translation of the Cd40 mRNA. Mice receiving thiamet G (TMG), an inhibitor of the O-GlcNAc hydrolase O-GlcNAcase, exhibited enhanced retinal protein O-GlcNAcylation and increased Cd40 mRNA translation. TMG administration also promoted Cd40 mRNA association with Müller-cell specific ribosomes isolated from the retina of RiboTag mice. Similar effects on O-GlcNAcylation and Cd40 mRNA translation were also observed in the retina of a mouse model of type 1 diabetes. In cultured cells, TMG promoted sequestration of the cap-binding protein eukaryotic translation in initiation factor 4E (eIF4E) by eIF4E-binding protein 1 (4E-BP1) and enhanced cap-independent Cd40 mRNA translation as assessed by a bicistronic reporter that contained the 5′-UTR of the Cd40 mRNA. Ablation of 4E-BP1/2 prevented the increase in Cd40 mRNA translation in TMG-exposed cells, and expression of a 4E-BP1 variant that constitutively sequesters eIF4E promoted reporter activity. Extending on the cell culture results, we found that in contrast to wild-type mice, diabetic 4E-BP1/2-deficient mice did not exhibit enhanced retinal Cd40 mRNA translation and failed to upregulate expression of the inflammatory marker nitric oxide synthase 2. These findings support a model wherein diabetes-induced O-GlcNAcylation of 4E-BP1 promotes Cd40 mRNA translation in Müller glia.

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Elevation in Circulating Soluble CD40 Ligand Concentrations in Type 2 Diabetic Retinopathy and Association with its Severity

Abstract: Plasma sCD40L levels were positively associated with DR. The significant finding here is that sCD40L levels can be predictors of DR severity.

Cited by 16 publications

References 37 publications

Endothelial Dysfunction in Diabetic Retinopathy

Endothelial Dysfunction in Diabetic Retinopathy

Evaluation of soluble CD40L in children with type 1 diabetes mellitus and its relation to diabetes associated vasculopathy

Diabetes enhances translation of Cd40 mRNA in murine retinal Müller glia via a 4E-BP1/2–dependent mechanism

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