Therapeutic effect of folic acid combined with decitabine in mice with diabetic retinopathy of different methylenetetrahydrofolate reductase(MTHFR)Geno-types
10.13389/j.cnki.rao.2025.0093
- VernacularTitle:叶酸联合地西他滨对不同亚甲基四氢叶酸还原酶(MTHFR)基因型糖尿病视网膜病变小鼠的治疗作用
- Author:
Yanru CHEN
1
;
Nian TAN
;
Xiaoxue HAN
;
Xifeng LIN
;
Yunyun HE
;
Xunwen LEI
Author Information
1. 730000 甘肃省兰州市,兰州大学第一临床医学院
- Publication Type:Journal Article
- Keywords:
diabetic retinopathy;
homocysteine;
5,10-methylenetetrahydrofolate reductase;
folic acid;
decitabine
- From:
Recent Advances in Ophthalmology
2025;45(7):533-538
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the therapeutic effect of folic acid combined with decitabine in diabetic retinop-athy(DR)mice with different methylenetetrahydrofolate reductase(MTHFR)genotypes.Methods The DR model mice were created by mating 20 MTHFR-/-mice with 20 wild-type C57 mice.A random number table method was employed to allocate 20 successfully modelled mice into the model group,DAC group,FA group,and FA+DAC group,with five mice assigned to each group.Five untreated MTHFR-/-and wild-type mice served as normal control.After constructing the DR model,the DAC group was injected intraperitoneally with 0.25 mg·kg-1 decitabine once every 5 days;the FA group was given 70 μg·kg-1 folic acid by tube feed once a day;the FA+DAC group was given 0.25 mg·kg-1 decitabine and 70μg·kg-1 folic acid at the same time;and the normal group was given an equal amount of physiological saline.All of the above groups were intervened for 30 days.OCT was employed for the measurement of retinal thickness,OCTA for retinal vascular density,histopathology(HE staining)for pathological changes in the mouse retina,real-time fluorescence quanti-tative PCR for mRNA expression,and Western blot analysis for protein expression levels.Results Compared with the wild-type model group,the degree of increase in retinal thickness and vascular density in the retinal layer was more pro-nounced in the MTHFR-/-mice model group(all P＜0.05).In wild-type mice,retinal thickness and retinal layer vessel den-sity were reduced in the DAC,FA and FA+DAC groups compared to the model group,with the FA+DAC group show-ing the greatest degree of reduction.The differences were all statistically significant(all P＜0.05);In MTHFR-/-mice,reti-nal thickness and vascular density in the retinal layer were reduced in the DAC group and the FA+DAC group compared to the model group(allP＜0.05).HE staining results showed an increased extent of retinal damage in the MTHFR-/-mice model group compared with the wild-type mice model group.Compared with the model group,the DAC group and the FA+DAC group had thinner retinas and more aligned ganglion cell layers in all types of mice,with the FA group having a worse effect and the FA+DAC group having a better treatment effect.The results of the polymerase chain reaction(PCR)revealed that the relative expression of the SAHH,MAT2A and DNMT1 proteins in the retinal tissues of the wildtype and MTHFR-/-mice model groups was elevated in comparison to the control group(all P＜0.05).Furthermore,the relative mR-NA expression of the DAC,FA and FA+DAC groups was reduced in comparison to the model group(all P＜0.05).In wild-type mice,the relative expression of MTHFR protein mRNA was decreased in the model group compared with the con-trol group,and increased in the DAC group,FA group,and FA+DAC group compared with the model group(all P＜0.05).Western blot results showed that the relative expression of DNMT1,MAT2A and SAHH proteins in the retinal tissues of the wild-type and MTHFR-/-mice model groups was higher than that of the control group(all P＜0.05),and the relative expression was lower in the DAC,FA,and FA+DAC groups compared with that in the model group(all P＜0.05).In wild-type mice,the relative expression of MTHFR protein in the retinal tissue of the model group was lower than that of the control group,and the relative expression of MTHFR protein in the FA group and the FA+DAC group was elevated com-pared with that of the model group(all P＜0.05).Conclusion The protective effect of folic acid combined with decit-abine on DR was superior to that of decitabine alone;treatment with folic acid in combination with decitabine may have yielded better efficacy in wild-type DR mice.
