PMID- 37717351
OWN - NLM
STAT- Publisher
LR  - 20231008
IS  - 1873-460X (Electronic)
IS  - 1056-8727 (Linking)
VI  - 37
IP  - 10
DP  - 2023 Oct
TI  - Protective effect of evolocumab on Muller cells in the rat retina under 
      hyperglycaemic and hypoxic conditions.
PG  - 108593
LID - S1056-8727(23)00191-5 [pii]
LID - 10.1016/j.jdiacomp.2023.108593 [doi]
AB  - AIMS: In this study, rat retinal Muller 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 CoCl(2) 
      and evolocumab on the cellular activity of RMCs was determined by CCK-8 assay. 
      The effect of CoCl(2) 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 CoCl(2) stimulation markedly 
      elevated PCSK9 and GFAP expression at the protein level in RMCs (P < 0.05). 
      Evolocumab treatment (100 mug/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-kappaB (NF-kappaB) 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-kappaB signalling pathway. Evolocumab may 
      be a promising anti-inflammatory therapy for ocular fundus diseases, such as DR.
CI  - Copyright (c) 2023 Elsevier Inc. All rights reserved.
FAU - Zhou, Qing
AU  - Zhou Q
AD  - Department of Ophthalmology, Changzhou Traditional Chinese Medicine Hospital, 
      Changzhou, China.
FAU - Tang, Huan
AU  - Tang H
AD  - Department of Ophthalmology, Changzhou Traditional Chinese Medicine Hospital, 
      Changzhou, China.
FAU - Li, Shuting
AU  - Li S
AD  - Department of Ophthalmology, The Third Affiliated Hospital of Soochow University, 
      Changzhou, China. Electronic address: lishuting1015@163.com.
LA  - eng
PT  - Journal Article
DEP - 20230830
PL  - United States
TA  - J Diabetes Complications
JT  - Journal of diabetes and its complications
JID - 9204583
SB  - IM
OTO - NOTNLM
OT  - Diabetic retinopathy
OT  - Evolocumab
OT  - Inflammation
OT  - Muller cells
OT  - TLR-4/NF-kappaB pathway
COIS- Declaration of competing interest The authors declare no conflicts of interest in 
      this work.
EDAT- 2023/09/18 00:41
MHDA- 2023/09/18 00:41
CRDT- 2023/09/17 18:03
PHST- 2023/02/19 00:00 [received]
PHST- 2023/07/30 00:00 [revised]
PHST- 2023/08/19 00:00 [accepted]
PHST- 2023/09/18 00:41 [pubmed]
PHST- 2023/09/18 00:41 [medline]
PHST- 2023/09/17 18:03 [entrez]
AID - S1056-8727(23)00191-5 [pii]
AID - 10.1016/j.jdiacomp.2023.108593 [doi]
PST - ppublish
SO  - J Diabetes Complications. 2023 Oct;37(10):108593. doi: 
      10.1016/j.jdiacomp.2023.108593. Epub 2023 Aug 30.