2. Academic Validation
  3. Protective effect of evolocumab on Müller cells in the rat retina under hyperglycaemic and hypoxic conditions

Protective effect of evolocumab on Müller cells in the rat retina under hyperglycaemic and hypoxic conditions

  • J Diabetes Complications. 2023 Oct;37(10):108593. doi: 10.1016/j.jdiacomp.2023.108593.
Qing Zhou 1,  Huan Tang 1,  Shuting Li 2
Affiliations

Affiliations

  • 1 Department of Ophthalmology, Changzhou Traditional Chinese Medicine Hospital, Changzhou, China.
  • 2 Department of Ophthalmology, The Third Affiliated Hospital of Soochow University, Changzhou, China. Electronic address: [email protected].
PMID: 37717351 DOI: 10.1016/j.jdiacomp.2023.108593
Abstract

Aims: In this study, rat retinal Müller cells (RMCs) were cultured in vitro to investigate the protective mechanism of evolocumab on rat RMCs in diabetes mellitus (DM) and the expression of relevant inflammatory factors.

Methods: The expression of proprotein convertase subtilisin/kexin type 9 (PCSK9) in the retinal tissues of diabetic rats was detected by immunohistochemistry. Sprague-Dawley (SD) rats at 5-7 d of life were selected as the source of RMCs and divided equally into three groups of 12 rats/24 eyes each. The effect of CoCl2 and evolocumab on the cellular activity of RMCs was determined by CCK-8 assay. The effect of CoCl2 and evolocumab on the migration level of RMCs after 72 h was measured by scratch test and the expression of various proteins after 72 h was measured by Western blot.

Results: In STZ rats, the expression of PCSK9 was significantly upregulated in the retina, especially in the inner nuclear layer, which is mainly composed of RMCs. High glucose and CoCl2 stimulation markedly elevated PCSK9 and GFAP expression at the protein level in RMCs (P < 0.05). Evolocumab treatment (100 μg/ml) reduced the expression and secretion of inflammatory factors in stimulated RMCs (P < 0.05). Furthermore, evolocumab downregulates toll-like receptor-4 (TLR-4) levels and inhibited nuclear transcription factor-κB (NF-κB) phosphorylation in RMCs (P < 0.05).

Conclusions: Evolocumab protects against inflammation in RMCs, at least in part, by negatively regulating the activation of the TLR-4/NF-κB signalling pathway. Evolocumab may be a promising anti-inflammatory therapy for ocular fundus diseases, such as DR.

Keywords

Diabetic retinopathy; Evolocumab; Inflammation; Müller cells; TLR-4/NF-κB pathway.

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