Fast Progression of Diabetic Retinopathy with SARS-CoV-2 Infection

Akduman, Yigit; Anderson, William A.; Saxena, Sandeep

doi:10.33590/emjdiabet/20-00254

Cited by 4 publications

(1 citation statement)

References 17 publications

(22 reference statements)

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“…48 49 These reports and our study certainly pinpoint the critical role of ACE2 in retinal pathology and pave the way for future studies in the context of DR and SARS-CoV-2. 50 Another exciting aspect of our study is improving the hematocrit and MCV after treatment with dapagliflozin, in line with published reports. 24 It is known that lower hemoglobin levels are associated with retinal ischemia and severity of DR, suggesting that low oxygen-carrying capacity is involved in the pathogenesis of DR; however, a mechanism could be complex and warrants further research towards multimodal action of dapagliflozin.…”

Section: Discussionsupporting

confidence: 85%

Dapagliflozin protects neural and vascular dysfunction of the retina in diabetes

Luo

Leley

Bello

et al. 2022

BMJ Open Diab Res Care

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IntroductionDapagliflozin, a sodium-glucose transporter inhibitor, effectively reduces blood glucose and is indicated for individuals with kidney diseases and cardiovascular disorders. In this study, we further expand the therapeutic benefit of dapagliflozin in the neural and vascular retina, with the potential to effectively manage diabetic retinopathy (DR), the most common complication of diabetes.Research design and methodsDb/db mice, an animal model of type 2 diabetes, were treated with dapagliflozin orally, and the electroretinogram (ERG) response and acellular capillary numbers were assessed. Messenger RNA levels of inflammatory cytokines were studied using real-time quantitative (q)PCR. We assessed endothelial cell migration in a scratch wound assay and retinal glucose uptake using human retinal endothelial cells.ResultsThe dapagliflozin treatment improved the ERG b-wave amplitude and decreased acellular capillary numbers. The scratch wound assay demonstrated a reduction in wound closure after dapagliflozin treatment. Retinal glucose uptake reduced after dapagliflozin treatment compared with the respective controls.ConclusionsOur studies suggest that dapagliflozin treatment effectively corrects neural and vascular dysfunction of the retina in diabetes. This effect is mediated by a decrease in inflammation and improved glycemic control. In addition, dapagliflozin exhibits decreased wound healing and glucose uptake, which could benefit the retina. Thus, dapagliflozin could be helpful in the management of DR, with multimodal therapeutic effects.

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Section: Discussionsupporting

confidence: 85%

Dapagliflozin protects neural and vascular dysfunction of the retina in diabetes

Luo

Leley

Bello

et al. 2022

BMJ Open Diab Res Care

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Relevance between COVID-19 and host genetics of immune response

Taher

Almaeen

Ghazy

et al. 2021

Saudi Journal of Biological Sciences

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The outbreak of coronavirus disease 2019 (COVID-19) was caused by the newly emerged corona virus (2019-nCoV alias SARS-CoV-2) that resembles the severe acute respiratory syndrome virus (SARS-CoV). SARS-CoV-2, which was first identified in Wuhan (China) has spread globally, resulting in a high mortality worldwide reaching ∼4 million deaths to date. As of first week of July 2021, ∼181 million cases of COVID-19 have been reported. SARS-CoV-2 infection is mediated by the binding of virus spike protein to Angiotensin Converting Enzyme 2 (ACE2). ACE2 is expressed on many human tissues; however, the major entry point is probably pneumocytes, which are responsible for synthesis of alveolar surfactant in lungs. Viral infection of pneumocytes impairs immune responses and leads to, apart from severe hypoxia resulting from gas exchange, diseases with serious complications. During viral infection, gene products (e.g. ACE2) that mediate viral entry, antigen presentation, and cellular immunity are of crucial importance. Human leukocyte antigens (HLA) I and II present antigens to the CD8 + and CD4 + T lymphocytes, which are crucial for immune defence against pathogens including viruses. HLA gene variants affect the recognition and presentation of viral antigenic peptides to T-cells, and cytokine secretion. Additionally, endoplasmic reticulum aminopeptidases (ERAP) trim antigenic precursor peptides to fit into the binding groove of MHC class I molecules. Polymorphisms in ERAP genes leading to aberrations in ERAP’s can alter antigen presentation by HLA class I molecules resulting in aberrant T-cell responses, which may affect susceptibility to infection and/or activation of immune response. Polymorphisms from these genes are associated, in global genetic association studies, with various phenotype traits/disorders some of which are related to the pathogenesis and progression of COVID-19; polymorphisms from various genes are annotated in genotype-tissue expression data as regulating the expression of ACE2, HLA’s and ERAP’s. We review such polymorphisms and illustrate variations in their allele frequencies in global populations. These reported findings highlight the roles of genetic modulators (e.g. genotype changes in ACE2 , HLA ’s and ERAP ’s leading to aberrations in the expressed gene products or genotype changes at other genes regulating the expression levels of these genes) in the pathogenesis of viral infection.

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