The effect of TC14012 on alkali burn-induced corneal neovascularization in mice.

To observe the effect of TC14012 (a CXCR4 antagonist and CXCR7 agonist) on alkali burn-induced corneal neovascularization (CNV) in a mouse model. CNV was induced in vivo by alkali burns on the corneas of BALB/c mice. A total of 54 mice treated with alkali burns were randomly divided into 3 groups, each of which received one of the following treatments: bilateral subconjunctival injections of TC14012 for 3 consecutive days, bilateral subconjunctival injections of balanced saline (BS) for 3 consecutive days or no treatment (blank control). The areas of CNV were measured on days 3, 7 and 14 after the alkali burns. CXCR4, CXCR7, vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP) mRNAs were detected and quantified by real-time reverse transcription PCR on days 7 and 14. Additionally, the expression of the proteins CXCR4, CXCR7, VEGF, β-arrestin 2, total ERK1/2 and phospho-ERK1/2 was determined by Western blotting. On day 7 after the alkali burns, the CNV area, VEGF, MMP-2 and MMP-9 mRNA levels, and VEGF, β-arrestin 2 and phospho-ERK1/2 protein levels were increased in the TC14012 group compared with the nontreatment and BS groups. However, on day 14, the CNV area, CXCR4, CXCR7, VEGF, MMP-2 and MMP-9 mRNA levels, and the CXCR4, CXCR7, VEGF and β-arrestin 2 protein levels were significantly decreased in the TC14012 group. TC14012 initially enhanced alkali burn-induced CNV but reduced CNV in later stages. In addition to CXCR4, CXCR7 is involved in the pathogenesis of CNV.

Shen M ，Yuan F ，Jin J ，Yuan Y ... -  《-》

Inhibitory effect of sub-conjunctival tocilizumab on alkali burn induced corneal neovascularization in rats.

Sari ES ，Yazici A ，Aksit H ，Yay A ，Sahin G ，Yildiz O ，Ermis SS ，Seyrek K ，Yalcin B ... -  《-》

Doxycycline enhances the inhibitory effects of bevacizumab on corneal neovascularization and prevents its side effects.

Su W ，Li Z ，Li Y ，Lin M ，Yao L ，Liu Y ，He Z ，Wu C ，Liang D ... -  《-》

Inhibitory effect of canstatin in alkali burn-induced corneal neovascularization.

To examine the effect of recombinant canstatin protein on the corneal neovascularization (CorNV) in an alkaline burn-induced CorNV model. This study involved 50 C57BL/6 mice. CorNV was induced by an alkaline burn of the corneas with 1 N NaOH under general anesthesia. Beginning 24 h after CorNV induction, recombinant canstatin protein was administered intraperitoneally at 5 or 10 mg/kg body weight once a day for up to 14 days. CorNV was evaluated by slit-lamp microscopy. Growth factors and cytokines relating to neovascularization and inflammation in the corneas were evaluated by real-time polymerase chain reaction (RT-PCR), Western blotting, immunohistochemistry or ELISA. Recombinant canstatin protein significantly inhibited CorNV. Compared to the untreated or PBS-treated CorNV group, expression of vascular endothelial growth factor (VEGF) markedly decreased in the canstatin-treated group as detected by various methods. Western blotting and RT-PCR showed that the canstatin treatment inhibited the expression of hypoxia-inducible factor and VEGF. Day 7 revealed the greatest changes: ELISA assay showed that TNF-α also significantly decreased in canstatin-treated corneas. Recombinant canstatin protein suppressed experimental CorNV, suggesting that canstatin may serve as a useful angiogenic inhibitor for the treatment of neovascularization-related corneal diseases.

Wang Y ，Yin H ，Chen P ，Xie L ，Wang Y ... -  《-》

KH902, a recombinant human VEGF receptor fusion protein, reduced the level of placental growth factor in alkali burn induced-corneal neovascularization.

To investigate the expression of placental growth factor (PIGF) in alkali burn-induced murine corneal neovascularization (NV); to evaluate the effects of KH902, a vascular endothelial growth factor receptor decoy, on prevention and regression of new vessels growths in the cornea; and to determine the influence of KH902 on the levels of vascular endothelial growth factor (VEGF) and PIGF in alkali burn-induced corneal NV. Mouse corneal NV was induced by alkali burn. The expression of PIGF was detected by immunohistochemistry and reverse-transcription polymerase chain reaction (RT-PCR). To evaluate the effects of KH902, corneal NV was observed and photographed every 3 days for a total of 28 days after the alkali burn. The percentage of NV area was measured and compared with that of the control group. The VEGF and PIGF levels in the cornea were evaluated by enzyme linked immunosorbent assay (ELISA). PIGF was expressed during the alkali burn-induced corneal neovascularization. On day 3 (D3), day 6 (D6) and day 9 (D9) after chemical cauterization, the length of the longest new vessel and the neovascularization areas in the KH902-treated groups were significantly smaller than those of the PBS-treated group (p < 0.05). The areas of established corneal NV of the KH902-treated groups regressed with time, but the control groups showed no natural regression. The VEGF and PIGF levels of the cornea in the treated groups were significantly decreased compared to those of the control group (p < 0.05). PIGF may be involved in alkali burn-induced corneal NV. KH902 significantly inhibited new vessel growth and promoted the regression of established vessels in a mouse model of corneal NV, and it also reduced the levels of VEGF and PIGF in the cornea.

Zhou AY ，Bai YJ ，Zhao M ，Yu WZ ，Li XX ... -  《-》