Effect Of Exogenous Mouse IP-10in Alkali Induced Corneal Neovascularization

Background and ObjectiveThe cornea is characterized by the absence of blood vessels under physiologicalconditions. Corneal avascularity is preserved by the balance between proangiogenic andantiangiogenic molecules and is required for optical clarity and visual acuity. Cornealneovascularization can arise from various causes, such as corneal inflammation, trauma,hypoxia and edema, which disrupt the balance between proangiogenic and antiangiogenicmolecules and can lead to severe impaired vision. It has been proved that as a chemokine,interferon-inducible protein-10(IP-10) can regulate the immuno-inflammatory reaction.Some researches showed that IP-10also played roles in regulating the neovascular vesselformation, such as inhibiting neovascularization, tumor growth and transfer, participatingvessel remodeling. Although corneal neovascularization (CNV) is associated with multiplecellular factors, the role of IP-10in CNV has remained obscure.Material and Methods1. The alkali burn induced CNV models were established by placing a2×2mm filterpaper saturated with1mol/L NaOH at the central corneas of the left eyes for40seconds.10mg/L IP-10was topically administered three times a day from the first day or14daysafter alkali injury in the early intervene group(10eyes) or middle-late intervene group(5eyes) respectively. CNV area was measured as a percentage of whole cornea.0.2%sodiumhyaluronate as vehicle was utilized in control group.2. Angiogenic factor expression in corneal tissue in the early intervene group wasquantified by reverse transcriptase polymerase chain reaction (RT-PCR) and compared tothose of control group.3. The intra-corneal infiltration of macrophages were detected by F4/80immunohistochemistry and compared between the early intervene and control group. Results1. The CNV percentage was (88.67±3.23)%in the control mice, showing a significantincrease in comparison with that of IP-10early intervene group (70.06±3.68)%(t=3.77,P=0.0013). On21days after corneal alkali burn, the CNV percentage was (87.33±5.50)%in the control mice, and that of the IP-10middle-late intervene group was (86.56±5.58)%without significant difference between them (t=1.26, P>0.05).2. Two days or four days after IP-10early intervene, the expressions of chemokinereceptor type3(CXCR3) in corneal tissue were significant higher than control group(t=3.13,3.07, P<0.05). The expressions of both vascular endothelial growth factor (VEGF)in cornea (t=5.99,6.27, P<0.01) and transforming growth factor-β1(TGF-β1)(t=8.50,P<0.01; t=4.53, P<0.05) in intervene group were significant impaired than control group.3. IP-10early intervention for two or four days had no significant effect on theintra-corneal infiltration of F4/80positive macrophages (t=1.65, P>0.05; t=0.59, P>0.05).ConclusionThe early topical administration of the exogenous mouse IP-10can inhibit CNV byup-regulating CXCR3expression and down-regulating VEGF and TGF-β1expression incornea, with no changes of macrophages infiltration. However, middle-later usage of theIP-10is ineffective.