Inhibitory effects of anti-vascular endothelial growth factor (VEGF) antibody MIL60 on alkali-induced corneal angiogenesis in rats / 眼科新进展

Objective To investigate the efficacy of an anti-vascular endothelial growth factor (VEGF) antibody,MIL60,in inhibiting corneal neovascularization (CoNV) formation in a rat model of alkali cauterization and its involved mechanisms.Methods Rat CoNV model induced by alkali burn was founded in the right eyes,and then 72 cases were randomly divided into four groups according to the subconjunctival administration of medicine next day after the successful establishment of this model:25mg· mL-1 MIL60 group,dexamethasone group,MIL60 solvent group and NaCl group.Then CoNV was observed for recording the its length and the involved area using digital photograph.Next the rats were sacrificed on day 7,14,21 and 28,followed by the collection of rats' cornea for HE and immunohistochemical staining to analyze the protein expression of VEGF,VEGF receptor-1 (VEGFR-1),VEGFR-2 and matrix metallopeptidase-9 (MMP-9).Results At each time point,the area and length of CoNV in the 25 mg· mL-1 MIL60 and dexamethasone group were significantly less than those in the MIL60 solvent and NaC1 group,and the differences were statistically significant (all P ＜0.01),and 25 mg· mL-1 MIL60 group had the similar CoNV area and length with the dexamethasone group (all P ＞ 0.05).Moreover,HE and immunohistochemical staining showed that MIL60 could inhibit the protein expression of VEGF,VEGFR-1,VEGFR-2 and MMP-9,which could explain its effective anti-angiogenic activity.Conclusion Subconjunctival administration of MIL60 can significantly inhibit corneal neovascularization formation and alleviate the inflammation in rats suffered from alkali burn.

Effect of quercetin on the scar formation after the alkal cauterization in rat's cornea / 西安交通大学学报(医学版)

Objective To explore the possible effect and mechanism of quercetin (QU) in inhibiting scar formation after the alkali burn of rat's cornea. Methods We established corneal alkali-burn model on right eyes of the SD rats. The rats were divided into five groups randomly. The control group received blank ophthalmic gel; the QU treatment groups received 2.5, 5, 10, or 20g/kg quercetin ophthalmic gel, respectively. The rats were checked by slit-lamp microscope every day for the degree of corneal opacity, then were killed on day 4, 7, 14, 21 and 28 after operation. The infiltration of the inflammatory cells was observed by histology, the arrangement and proliferation of the collagen fibers in the corneal stroma were observed by Masson trichrome staining. The expression of transforming growth factor-β_1 (TGF-β_1) and receptor of transforming growth factor-βⅠ(TGF-βRⅠ) in cornea was observed by immunohistochemical method. Results The corneal opacity was less severe in the QU treatment groups than in the control group (P<0.05). Corneal scar was inhibited better in 10g/kg QU and 20g/kg QU groups than in 2.5g/kg and 5g/kg QU groups, and 10g/kg and 20g/kg QU groups had no significant differences (P>0.05). HE and Masson staining showed that the density of corneal stroma collagen fibers in the QU treatment groups was lower than that in the control group. The expression of TGF-β_1 and TGF-βRⅠ reached the peak on day 7 after alkali burn, and then decreased slowly, which was close to the normal level. The expression of TGF-β_1 and TGF-βRⅠ was inhibited better in 10g/kg and 20g/kg QU groups than in 2.5g/kg and 5g/kg groups, and 10g/kg and 20g/kg QU groups had no significant differences (P>0.05). Conclusion QU ophthalmic gel can reduce formation of corneal scar to a certain extent, 10g/kg is the optimal concentration. QU may play its role by inhibiting the expression of TGF-β1 and TGF-βRⅠ.