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Article

Distinct Mechanisms of Human Retinal Endothelial Barrier Modulation In Vitro by Mediators of Diabetes and Uveitis

1
Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta, GA 30912, USA
2
Research Division, Charlie Norwood VA Medical Center, Augusta, GA 30912, USA
3
Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA
4
Vision Discovery Institute, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA
*
Authors to whom correspondence should be addressed.
Academic Editors: Hossam Ashour and Robert Gabriel
Life 2022, 12(1), 33; https://doi.org/10.3390/life12010033
Received: 8 November 2021 / Revised: 30 November 2021 / Accepted: 10 December 2021 / Published: 27 December 2021
(This article belongs to the Section Physiology and Pathology)
Ocular diseases such as diabetic retinopathy (DR) and uveitis are associated with injury to the blood–retinal barrier (BRB). Whereas high glucose (HG) and advanced glycation end products (AGE) contribute to DR, bacterial infections causing uveitis are triggered by endotoxins such as lipopolysaccharide (LPS). It is unclear how HG, AGE, and LPS affect human retinal endothelial cell (HREC) junctions. Moreover, tumor necrosis factor-α (TNFα) is elevated in both DR and ocular infections. In the current study, we determined the direct effects of HG, AGE, TNFα, and LPS on the expression and intracellular distribution of claudin-5, VE-cadherin, and β-catenin in HRECs and how these mediators affect Akt and P38 MAP kinase that have been implicated in ocular pathologies. In our results, whereas HG, AGE, and TNFα activated both Akt and P38 MAPK, LPS treatment suppressed Akt but increased P38 MAPK phosphorylation. Furthermore, while treatment with AGE and HG increased cell-junction protein expression in HRECs, LPS elicited a paradoxical effect. By contrast, when HG treatment increased HREC-barrier resistance, AGE and LPS stimulation compromised it, and TNFα had no effect. Together, our results demonstrated the differential effects of the mediators of diabetes and infection on HREC-barrier modulation leading to BRB injury. View Full-Text
Keywords: blood–brain barrier; claudin-5; AGE; TNFα; hyperglycemia; lipopolysaccharide blood–brain barrier; claudin-5; AGE; TNFα; hyperglycemia; lipopolysaccharide
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MDPI and ACS Style

Rudraraju, M.; Narayanan, S.P.; Somanath, P.R. Distinct Mechanisms of Human Retinal Endothelial Barrier Modulation In Vitro by Mediators of Diabetes and Uveitis. Life 2022, 12, 33. https://doi.org/10.3390/life12010033

AMA Style

Rudraraju M, Narayanan SP, Somanath PR. Distinct Mechanisms of Human Retinal Endothelial Barrier Modulation In Vitro by Mediators of Diabetes and Uveitis. Life. 2022; 12(1):33. https://doi.org/10.3390/life12010033

Chicago/Turabian Style

Rudraraju, Madhuri, S. P. Narayanan, and Payaningal R. Somanath. 2022. "Distinct Mechanisms of Human Retinal Endothelial Barrier Modulation In Vitro by Mediators of Diabetes and Uveitis" Life 12, no. 1: 33. https://doi.org/10.3390/life12010033

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