PMID- 37577690
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240502
DP  - 2023 Aug 4
TI  - Retinoid X Receptor activation prevents diabetic retinopathy in murine models.
LID - 2023.08.03.551887 [pii]
LID - 10.1101/2023.08.03.551887 [doi]
AB  - Previously, the RXR agonist UAB126 demonstrated therapeutic potential to treat 
      obese mice by controlling blood glucose levels (BGL) and altering the expression 
      of genes associated with lipid metabolism and inflammatory response. The purpose 
      of the study was to assess UAB126 effect in progression of diabetic retinopathy 
      (DR) in rodent models of Type1 diabetes (T1D), streptozotocin-induced, and Type2 
      diabetes (T2D), the db/db mice. UAB126 treatment was delivered either by oral 
      gavage for 6 weeks or by topical application of eye drops for 2 weeks. At the end 
      of the treatment, the retinal function of diabetic mice was assessed by 
      electroretinography (ERG), and their retinal tissue was harvested for protein and 
      gene expression analyses. Bone-marrow cells were isolated and differentiated into 
      bone marrow-derived macrophages (BMDMs). The glycolysis stress test and the 2-DG 
      glucose uptake analysis were performed. Our results demonstrated that in the 
      UAB126-treated diabetic BMDMs, the ECAR rate and the 2-DG uptake were improved as 
      compared to untreated diabetic BMDMs. In UAB126-treated diabetic mice, 
      hyperglycemia was reduced and associated with the preservation of ERG amplitudes 
      and enhanced AMPK activity. Retinas from diabetic mice treated with topical 
      UAB126 demonstrated an increase in Rxr and Ppar, and expression of genes 
      associated with lipid metabolism. Altogether, our data indicate that RXR 
      activation is beneficial to preclinical models of DR.
FAU - Dorofeeva, Iuliia
AU  - Dorofeeva I
AD  - Department of Optometry and Vision Science, School of Optometry, University of 
      Alabama at Birmingham, Birmingham, Alabama, USA.
FAU - Zhylkibayev, Assylbek
AU  - Zhylkibayev A
AD  - Department of Optometry and Vision Science, School of Optometry, University of 
      Alabama at Birmingham, Birmingham, Alabama, USA.
FAU - Saltykova, Irina V
AU  - Saltykova IV
AD  - Department of Optometry and Vision Science, School of Optometry, University of 
      Alabama at Birmingham, Birmingham, Alabama, USA.
FAU - Atigadda, Venkatram
AU  - Atigadda V
AD  - Heersink School of Medicine, Department of Dermatology, University of Alabama at 
      Birmingham, Birmingham, Alabama, USA.
FAU - Adhikari, Bibek
AU  - Adhikari B
AD  - Department of Optometry and Vision Science, School of Optometry, University of 
      Alabama at Birmingham, Birmingham, Alabama, USA.
FAU - Gorbatyuk, Oleg
AU  - Gorbatyuk O
AD  - Department of Optometry and Vision Science, School of Optometry, University of 
      Alabama at Birmingham, Birmingham, Alabama, USA.
FAU - Grant, Maria B
AU  - Grant MB
AD  - Heersink School of Medicine, Department of Ophthalmology and Vision Sciences, 
      University of Alabama at Birmingham, Birmingham, Alabama, USA.
FAU - Gorbatyuk, Marina
AU  - Gorbatyuk M
AD  - Department of Optometry and Vision Science, School of Optometry, University of 
      Alabama at Birmingham, Birmingham, Alabama, USA.
LA  - eng
GR  - P30 DK056336/DK/NIDDK NIH HHS/United States
GR  - P30 DK079626/DK/NIDDK NIH HHS/United States
GR  - P30 EY003039/EY/NEI NIH HHS/United States
PT  - Preprint
DEP - 20230804
PL  - United States
TA  - bioRxiv
JT  - bioRxiv : the preprint server for biology
JID - 101680187
UIN - Cells. 2023 Sep 26;12(19):. PMID: 37830574
PMC - PMC10418239
EDAT- 2023/08/14 06:43
MHDA- 2023/08/14 06:44
PMCR- 2023/08/11
CRDT- 2023/08/14 05:03
PHST- 2023/08/14 06:43 [pubmed]
PHST- 2023/08/14 06:44 [medline]
PHST- 2023/08/14 05:03 [entrez]
PHST- 2023/08/11 00:00 [pmc-release]
AID - 2023.08.03.551887 [pii]
AID - 10.1101/2023.08.03.551887 [doi]
PST - epublish
SO  - bioRxiv [Preprint]. 2023 Aug 4:2023.08.03.551887. doi: 10.1101/2023.08.03.551887.