Therapeutic effect of folic acid combined with decitabine on diabetic mice.

AIM: To evaluate the therapeutic effect of folic acid combined with decitabine on diabetic mice. METHODS: The diabetic model of db/db mice were randomly divided into model group, folic acid group, decitabine group, folic acid combined with decitabine group, and C57 mice as normal control group. The density of retinal blood vessels and retinal thickness were detected by fundus photography and optical coherence tomography, respectively. Pathological changes of retina were observed by hematoxylin-eosin (HE) staining. The homocysteine (Hcy) in serum was detected by enzyme linked immunosorbent assay (ELISA). TdT-mediated dUTP nick-end labeling (TUNEL) was used to detect apoptosis in retinal tissue. Evans blue dye was used to detect the permeability of retinal blood vessels. The platelet endothelial cell adhesion molecule-1 (CD31) and vascular endothelial growth factor receptor (VEGFR) protein were detected by Western blot. The 3-nitrotyrosine (3-NT) and 4-hydroxynonanine (4-HNE) were detected by immunohistochemistry. RESULTS: The density of retinal blood vessels, retinal thickness, retinal vascular permeability and the proportion of apoptotic cells of retinal tissue in the model group increased significantly than control group (P<0.05). The Hcy in serum and the levels of CD31, VEGFR, 3-NT, and 4-HNE in retinal tissue increased significantly in the model group (P<0.01). Folic acid and decitabine both reversed these changes significantly, and the combination of the folic acid and decitabine worked best. CONCLUSION: The combination of folic acid and decitabine has a more significant protective effect on the retina in diabetic mice.

The Protective Roles of Folic Acid in Preventing Diabetic Retinopathy Are Potentially Associated with Suppressions on Angiogenesis, Inflammation, and Oxidative Stress.

This study aimed to evaluate the therapeutic effect of folic acid (FA) on diabetic retinopathy (DR) in a genetic mouse model of obese type 2 diabetes mellitus (T2D). C57BL/KsJ-db/db (db/db) T2D mice were divided into control, FA, metformin (MET), and FA plus MET groups (n = 10/group). Serum levels of glucose, glycated hemoglobin, and insulin were determined weekly. The retinal thickness was measured using optical coherence tomography (OCT) at 4 weeks after treatments. The retinal expression and serum levels of vascular formation, inflammation, and oxidative stress-associated molecules were examined. Our results demonstrated that FA, but not MET, played a protective role against retinal thinning in the early stage of DR in db/db mice, although FA did not exhibit antihyperglycemic effect. In addition, retinal expression and serum levels of a panel of molecules associated with angiogenesis (CD31 and VEGFR), inflammation (IL-1ß and NLRP3), and oxidative stress (3-NT, 4-HNE, Vav2, and NOX4) were significantly downregulated in FA-treated diabetic mice compared with those in saline-treated controls. Furthermore, the serum level of homocysteine was also markedly decreased following FA treatments. These findings suggest that through potential suppressions on angiogenesis, inflammation, and oxidative stress, FA may serve as a potential therapeutic agent against DR.

[Changes of structures of anterior chamber angle in rabbit chronic high intraocular pressure model].

OBJECTIVE: To observe the anterior chamber angle changes occurred in compound Carbomer-induced chronic high intraocular pressure (IOP) model in rabbit eyes. METHODS: It was an experimental study. Thirty two rabbits were randomly divided into eight groups. Compound Carbomer (0.3%, 0.3 ml) was injected into the left anterior chamber. A group of rabbits were randomly killed after 1, 2, 3, 4, 6, 8, 10 and 12 weeks. The anterior chamber of the rabbit eye specimens was observed. RESULTS: IOP increased slowly following the application of the drug, high IOP lasted for 3 months. The drug-induced changes of anterior chamber angle consisted of early inflammatory response and late fibrous changes. Inflammatory response occurred in early stage and reduced or disappeared after 3 weeks. Fibrous degeneration and adhesion obstruction occurred in the anterior chamber angle after 4 weeks. Under the electron microscope, the trabecular was expanded and deformed, with hyperplasia of collagen and elastic fibers. Endothelial cells were separated from the trabecular, and showed the morphology of lymphocytes, with the function similar to the macrophages. Phagocytized Carbomer particles were transported through the vacuoles of Schlemm's canal endothelial cells. Large vacuoles gradually reduced. Excessive Carbomer particles were accumulated in the endothelial cells and obstructed the Schlemm's canal. This induced the fibrous proliferation and the destruction of anterior chamber angle structures. CONCLUSIONS: The obstruction of aqueous humor outflow induced by compound Carbomer in rabbit high IOP model is caused mainly by the changes in trabecular endothelial cells.

[Effects of butyrylchitosan on expression of proliferating cell nuclear antigen in fibroblast proliferation of rabbit eyes after filtering operation].

OBJECTIVE: To investigate the effect of butyrylchitosan on the expression of proliferating cell nuclear antigen ( PCNA) in fibroblast proliferation of rabbit eyes after filtering operation. METHODS: Twenty-four New Zealand rabbits were randomly divided into 2 groups, with 12 rabbits in each group. Rabbits in one group received butyrylchitosan under scleral patch of trabeculectomy in right eyes and trabeculectomy in left eyes (trabeculectomy group). Rabbits in the other group received mitomycin C (MMC) in trabeculectomy in right eyes (MMC group) and without operation in left eyes. Rabbits were killed 1, 4, and 12 weeks after operations. Immunohistochemical staining was used to detected PCNA expression in fibroblast. RESULTS: After use of butyrylchitosan, the PCNA expression significantly decreased compared with trabeculectomy group (P < 0. 001). PCNA expression in MMC group was significantly lower than in trabeculectomy group (P <0. 001). CONCLUSION: Using butyrylchitosan under scleral patch of trabeculectomy decreases PCNA expression in proliferating cell and inhibits the scarring at filtering site.