Plasminogen kringle 5 inhibits alkali-burn-induced corneal neovascularization.

Plasminogen kringle 5 (K5) is a potent angiogenic inhibitor. The purpose of the present study was to evaluate the therapeutic effect of K5 on alkali-burn-induced corneal neovascularization (NV) and to investigate its mechanism of action. Corneal NV was induced in rabbits by NaOH. The rabbits received eye drops containing K5 or vehicle alone, four times per day. Corneal NV and inflammation were monitored every other day with a slit lamp microscope, and the length of the vessels in the cornea and the area of NV were measured. Vascular endothelial growth factor (VEGF) was determined by immunohistochemical and Western blot analyses. The TUNEL assay was used to assess the apoptosis of endothelial cells. The effects of K5 on primary bovine aortic endothelial cells (BAECs) were determined by MTT assay, flow cytometry, transmission electron microscopy, and DNA fragmentation assay. Alkali-burn-induced progressive corneal NV and inflammation in the cornea. K5 delayed the onset of corneal NV (P < 0.05) and decreased NV areas (P < 0.05) in a dose-dependent manner. K5 treatment, after the formation of corneal NV, induced regression of newly formatted vessels in the cornea. K5 decreased the inflammatory index in the corneas at different time points after the alkali burn. Corneal VEGF levels were reduced by K5 treatment. K5 inhibits proliferation and induces apoptosis in BAECs. Topical application of K5 may have therapeutic potential for the chemical burn-induced corneal NV and inflammation. The inhibitory effect of K5 on corneal NV may be by downregulation of VEGF expression.

Zhang Z ，Ma JX ，Gao G ，Li C ，Luo L ，Zhang M ，Yang W ，Jiang A ，Kuang W ，Xu L ，Chen J ，Liu Z ... -  《INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE》

Acidic/neutral amino acid residues substitution in NH2 terminal of plasminogen kringle 5 exerts enhanced effects on corneal neovascularization.

Li C ，Li L ，Cheng R ，Dai Z ，Li C ，Yao Y ，Zhou T ，Yang Z ，Gao G ，Yang X ... -  《-》

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 ... -  《-》

Alkali burn-induced synthesis of inflammatory eicosanoids in rabbit corneal epithelium.

Conners MS ，Urbano F ，Vafeas C ，Stoltz RA ，Dunn MW ，Schwartzman ML ... -  《INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE》

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 ... -  《-》