Nitazoxanide Reduced Inflammatory Markers and Mitochondrial Changes in Human Retinal Endothelial Cells Grown in High Glucose

Document Type

Article

Publication Date

1-1-2025

Publication Title

Molecular vision [electronic resource]

Abstract

PURPOSE: To determine whether nitazoxanide (NZT) can increase mitochondrial nuclear retrograde regulator 1 (MNRR1) in retinal endothelial cells (RECs) grown in normal or high glucose and thereby reduce inflammation.

METHODS: We used control and diabetic human retinal protein samples, control and diabetic mouse retinal samples, and RECs grown in normal (5 mM) and high (25 mM) glucose protein samples to explore levels of MNRR1, high mobility group box 1, interleukin 1β, tumor necrosis factor α, and Tom20 by western blotting. We used immunostaining to localize MNRR1 in the retina. We also used a Seahorse XF

RESULTS: MNRR1 protein levels were reduced in the diabetic retina of both humans and mice. MNRR1 was localized to RECs. RECs grown in normal or high glucose and treated with NZT had significantly higher MNRR1 levels. NZT reduced inflammatory markers in RECs grown in high glucose. NZT increased the oxygen consumption rate in RECs grown in high glucose, which was associated with an increase in Tom20.

CONCLUSIONS: MNRR1 is reduced in the diabetic retina. NZT increased MNRR1 levels in RECs. NZT protected RECs grown in high glucose by reducing inflammatory mediators and mitochondrial dysfunction and increasing mitochondrial mass. NZT may offer a new therapeutic option for diabetic retinopathy.

Volume

31

First Page

351

Last Page

357

ISSN

1090-0535

PubMed ID

41867367

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