Ameliorative effects of the liver X receptor agonist T0901317 on retinal struc-ture and function damage induced by high glucose in mice
10.13389/j.cnki.rao.2025.0080
- VernacularTitle:肝脏X受体激动剂T0901317对高糖所致的小鼠视网膜结构和功能损伤的改善作用
- Author:
Yongping TANG
1
;
Daosen CHEN
;
Jing CHEN
Author Information
1. 325000 浙江省温州市,温州医科大学附属眼视光医院
- Publication Type:Journal Article
- Keywords:
diabetic retinopathy;
liver X receptor;
T0901317;
inflammasome
- From:
Recent Advances in Ophthalmology
2025;45(6):457-462
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the ameliorative effects of the liver X receptor(LXR)agonist T0901317 on reti-nal structure and function damage caused by high glucose in mice.Methods A total of 30 12-week-old male C57BL/6J mice were randomly divided into the control,STZ-DMSO,and STZ-T0901317 groups,with 10 mice in each group.After a 12-hour fast,the mice were intraperitoneally injected with streptozotocin(STZ)at a dosage of 50 mg·kg-1 for 5 days.The mice in the control group were intraperitoneally injected with an equal volume of citrate buffer.The random blood glucose level was measured 72 hours after injection,and mice with the random blood glucose level exceeding 16.7 mmol·L-1 and polyuria were considered successful model candidates.These model mice were included in the STZ-DMSO and STZ-T0901317 groups,respectively,and the mice in the two groups were intravitreally injected with 1 μL of DMSO and 1 μL of T0901317(30 μmol·L-1),respectively.The thickness of the retinal nerve fiber layer(RNFL)was measured at 100 μm,200 μm,300 μm,400 μm,and 500 μm from the optic disc 6 weeks after STZ modeling.The cell density of the ganglion cell layer(GCL)(cells·mm-1)was quantified using ImageJ.Electroretinogram(ERG)analyses were employed to record the amplitude and latency of dark-adapted 0.01 ERG b-wave,dark-adapted 3.0 ERG a-and b-waves,dark-adapted 3.0 oscilla-tory potentials(OPs),and light-adapted 3.0 ERG a-and b-waves.The quantitative reverse transcription polymerase chain reaction(qRT-PCR)was used to detect the expression changes of inflammatory factors NLRP3,Caspase1,interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)in the retinal tissue of mice from each group.Results The optical coherence tomography(OCT)findings indicated that the RNFL thickness measured at 100 μm,200 μm,300μm,400 μm,and 500 μm from the optic disc in the STZ-DMSO group was significantly lower than that observed in the con-trol group,and the differences were statistically significant(all P＜0.05).In the STZ-T0901317 group,the RNFL thickness at all measurement points was greater than that in the STZ-DMSO group,and the differences were statistically significant(all P＜0.05).However,there were no statistically significant differences in the RNFL thickness at all measurement points between the STZ-T0901317 group and the control group(all P＞0.05).The hematoxylin and eosin(HE)staining results re-vealed that the GCL cell count in the control,STZ-DMSO,and STZ-T0901317 groups was(90.53±9.13)cells·mm-1,(82.06±0.98)cells·mm-1,and(94.94±10.61)cells·mm-1,respectively,with no significant differences among these groups(P＞0.05).The ERG results demonstrated that the amplitude of dark-adapted 0.01 ERG b-wave,dark-adapted 3.0 ERG a-and b-waves,the second wave of dark-adapted 3.0 oscillatory potentials(OPs2),and light-adapted ERG a-and b-waves was lower in the STZ-DMSO and STZ-T0901317 groups compared with the control group,and the differences were statistically significant(all P＜0.05).However,in the STZ-T0901317 group,the amplitude of dark-adapted 3.0 ERG a-and b-waves and OPs2 was higher than that in the STZ-DMSO group,and the differences were statistically significant(all P＜0.05).qRT-PCR analyses revealed that in the STZ-DMSO group,the relative mRNA expression level of NLRP3,Caspase-1,IL-1β,and IL-6 was elevated compared with the control group,and the differences were statistically significant(all P＜0.05).The relative mRNA expression level of NLRP3 and IL-6 in the STZ-T0901317 group was higher compared with the control group,and the differences were statistically significant(both P＜0.05).The relative mRNA expression level of NLRP3,Caspase-1,and IL-1β in the STZ-T0901317 group decreased compared with the STZ-DMSO group,and the differences were statistically significant(all P＜0.05).Conclusion The LXR agonist T0901317 may ameliorate early RNFL thickness alterations and im-prove visual function in DR mice by down-regulating the expression of NLRP3,Caspase-1,and IL-1β in mouse retinal tissues.
