PMID- 37830574
OWN - NLM
STAT- MEDLINE
DCOM- 20231023
LR  - 20240210
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 12
IP  - 19
DP  - 2023 Sep 26
TI  - Retinoid X Receptor Activation Prevents Diabetic Retinopathy in Murine Models.
LID - 10.3390/cells12192361 [doi]
LID - 2361
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 the effects of UAB126 on the progression of diabetic 
      retinopathy (DR) in rodent models of type 1 diabetes (T1D), 
      streptozotocin-induced, and type 2 diabetes (T2D), in 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 the 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, AL 35233, USA.
FAU - Zhylkibayev, Assylbek
AU  - Zhylkibayev A
AUID- ORCID: 0000-0001-9244-1505
AD  - Department of Optometry and Vision Science, School of Optometry, University of 
      Alabama at Birmingham, Birmingham, AL 35233, USA.
FAU - Saltykova, Irina V
AU  - Saltykova IV
AD  - Department of Optometry and Vision Science, School of Optometry, University of 
      Alabama at Birmingham, Birmingham, AL 35233, USA.
FAU - Atigadda, Venkatram
AU  - Atigadda V
AD  - Department of Dermatology, Heersink School of Medicine, University of Alabama at 
      Birmingham, Birmingham, AL 35233, USA.
FAU - Adhikari, Bibek
AU  - Adhikari B
AUID- ORCID: 0000-0002-9615-8923
AD  - Department of Optometry and Vision Science, School of Optometry, University of 
      Alabama at Birmingham, Birmingham, AL 35233, USA.
FAU - Gorbatyuk, Oleg S
AU  - Gorbatyuk OS
AD  - Department of Optometry and Vision Science, School of Optometry, University of 
      Alabama at Birmingham, Birmingham, AL 35233, USA.
FAU - Grant, Maria B
AU  - Grant MB
AD  - Department of Ophthalmology and Vision Sciences, Heersink School of Medicined, 
      University of Alabama at Birmingham, Birmingham, AL 35233, USA.
FAU - Gorbatyuk, Marina S
AU  - Gorbatyuk MS
AUID- ORCID: 0000-0001-9060-856X
AD  - Department of Optometry and Vision Science, School of Optometry, University of 
      Alabama at Birmingham, Birmingham, AL 35233, USA.
LA  - eng
GR  - R01 EY027763/EY/NEI NIH HHS/United States
GR  - R01 CA276683/CA/NCI NIH HHS/United States
GR  - P30 DK079626/DK/NIDDK NIH HHS/United States
GR  - P30 EY003039/EY/NEI NIH HHS/United States
GR  - P30 DK056336/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20230926
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
RN  - 0 (Retinoid X Receptors)
SB  - IM
UOF - bioRxiv. 2023 Aug 04;:. PMID: 37577690
MH  - Mice
MH  - Animals
MH  - *Diabetic Retinopathy/drug therapy/prevention & control/metabolism
MH  - Retinoid X Receptors
MH  - *Diabetes Mellitus, Type 2/metabolism
MH  - *Diabetes Mellitus, Experimental/metabolism
MH  - Disease Models, Animal
PMC - PMC10571672
OTO - NOTNLM
OT  - UAB126
OT  - diabetic retinopathy
OT  - murine model
OT  - retinoid X receptor
COIS- The authors declare no conflict of interest.
EDAT- 2023/10/13 12:44
MHDA- 2023/10/23 01:18
PMCR- 2023/09/26
CRDT- 2023/10/13 08:13
PHST- 2023/08/18 00:00 [received]
PHST- 2023/09/20 00:00 [revised]
PHST- 2023/09/22 00:00 [accepted]
PHST- 2023/10/23 01:18 [medline]
PHST- 2023/10/13 12:44 [pubmed]
PHST- 2023/10/13 08:13 [entrez]
PHST- 2023/09/26 00:00 [pmc-release]
AID - cells12192361 [pii]
AID - cells-12-02361 [pii]
AID - 10.3390/cells12192361 [doi]
PST - epublish
SO  - Cells. 2023 Sep 26;12(19):2361. doi: 10.3390/cells12192361.