Table 1.
Novel agents, with potential antiangiogenic effects, used for treatment of corneal neovascularization in animal models.
| Agentref | Model | Route | Proposed Mechanism(s) |
|---|---|---|---|
| Diospyros kaki Extract (EEDK)309 | Alkali burn | Oral | Suppression of VEGF, FGF, IL-6, and MMP-2. |
| Recombinant PEDF310 | Chemical injury | S.C. | Inhibits VEGF, bFGF and IL-8. |
| PEDF311 | Chemical injury | Topical | Downregulates VEGF expression. |
| Gold nanoparticles312 | Chemical injury | Topical | Decreases VEGFR-2 levels, inhibits ERK phosphorylation. |
| interferon-induced protein of 10 kDa (IP-10)313 | Chemical injury | Topical | Decreases VEGF and bFGF expression, EC proliferation and tube formation. |
| Netrin 1314 | Chemical injury | Topical | Laminin-related protein; Decrease inflammation, decrease VEGF, increase PEDF. |
| Netrin-4315 | Chemical injury | Topical | Laminin-related protein Decreases leukocyte infiltration and VEGF and NF-κB signaling and EC migration, invasion and tube formation, increases PEDF. |
| LCB54–0009316 | Suture induced and chemical injury | S.C. | Imidazole-based alkaloid Derivative; Antioxidant; decreases VEGF-A and HIF-1α level, inhibits VEGFR-2 and NF-κB signaling, decrease MMP-1, −2, −3 and −9 activity. |
| Epigallocatechin gallate317 | Suture induced | Topical | Flavonoid; Decreases expression of VEGF and COX-2. |
| Largazole318 | Chemical injury | Topical | Histone deacetylase inhibitor; Decreases expression of VEGF, b-FGF, TGFβ1 and EGF. |
| Serine Proteinase Inhibitor A3K (SERPINA3K)319 | Suture induced | Topical | Inhibits Wnt signaling pathway and VEGF |
| TC14012320 | Chemical injury | S.C. | CXCR4 antagonist and CXCR7 agonist; Reduce CXCR4, CXCR7, VEGF and MMP-2 and −9 mRNA levels* |
| Itraconazole321 | Chemical injury | Topical, S.C., I.P. | Inhibits cholesterol biosynthesis, endothelial cell proliferation and capillary tube formation. |
| Lanepitant322 | Chemical injury and Suture induced | Topical | NK1 receptor antagonist; Reduces corneal substance P level and leukocyte infiltration. |
| Low-molecular-weight heparin-taurocholate 7 (LHT7)323 | Chemical injury | S.C. | Blocks VEGF-VEGFR. |
| Recombinant C-terminal fragment BIGH3 protein324 | Micropocket assay | Local | Blocks phosphorylation of PI3K/Akt and ERK, inhibits tube formation, increase EC apoptosis. |
| Celastrol325 | Suture induced | Topical | Reduce the expression of VEGF, MMP-9, and MCP-1. |
| ADP-ribosylation factor326 | Chemical injury | Topical | Ras-related small GTPase; Downregulates corneal VEGF expression, increases EC apoptosis. |
| SB-328437327 | Chemical injury | Topical | CCR3 antagonist; Reduces intracorneal MCP-1 and MCP-3 mRNA expression. |
| Ascorbic acid328 | Suture induced | Topical | Anti-VEGF and anti-MMP. |
| Cetuximab329 | Chemical injury | S.C. | Anti-EGFR mab; Inhibits EGFR, modulate VEGF and IL-8. |
| Peroxiredoxin-6330 | Ultraviolet radiation | Topical | Anti-oxidant; Inhibits NF-κB, decrease VEGF expression, increase PEDF expression. |
| CL9189AP331 | Chemical injury | Anti-SDF-α1 mab; Inhibits SDF-α1/CXCR4 pathway, down regulates VEGF and C-Kit expression. | |
| Methotrexate332 | Suture induced | Topical, S.C. | Cytotoxic agent; Decreases VEGF and IL-6 expression. |
| N-acetyl-L-cysteine333 | Chemical injury | I.P. | Anti-oxidant; Down-regulates NF-κB pathway. |
| Suramab334 | Chemical injury | I.V. | Combined Bevacizumab and Suramin; Inhibits VEGF, bFGF, PDGF, IGF, TGF-β. |
| Canstatin335 | Chemical injury | I.P. | NC1 domain of the α2 chain of type IV collagen; Inhibits VEGF, HIF-α and TNF-α, prevents EC migration and tube formation. |
| AMD3100336 | Chemical injury | S.C. | Antagonist of CXCR4; Decreases inflammation, VEGFR-2 expression and EC proliferation. |
| Dihydroartemisinin337 | Suture induced | Topical | Novel anti-malarial drug; Reduces expression of and phosphorylation of VEGF and VEGFR-2, ERK1/2 and p38. |
| Parstatin338 | Chemical injury | S.C. | Proteinase-activated receptor 1; Inhibits FGF-2, VEGF, ERK1/2 and MAPK. |
| PTK/ZK, ZK991339 | Suture induced | Oral | VEGFR-tyrosine kinase inhibitors; Block VEGF receptors. |
| IMD0354340 | Suture induced | Systemic | Selective blocker of the IKK complex IκB kinase β (IKK2). Decreases inflammatory cell invasion, suppressed CCL2, CXCL5, Cxcr2, and TNF-a and VEGF-A expression. |
| IL-1R antagonist341 | Suture induced | Topical | Inhibits IL-1 induced angiogenesis. |
| H-KI20342 | Suture induced and Micropocket assay | Topical | A 20-amino acid peptide from HGF with anti-inflammatory and antiangiogenic preoperties. |
| Angiopoietin-like protein 2 (ANGPTL2)343 | Chemical injury | Topical | Short heparin RNA inhibiting ANGPTL2 induced inflammation and angiogenesis. |
| Tissue inhibitors of matrix metalloproteinases344 | Micropocket assay | Topical | Inhibits proliferation and migration of human ECs. |
| suberoylanilide hydroxamic acid (SAHA)345 | Chemical injury | Topical | Downregulates the expression of VEGF, bFGF, TGFβ1 and EGF and inhibits migration, proliferation, and tube formation by ECs. |
| Suramin346 | Suture induced | S.C. | Heparin analog; Decreases expression of VEGF, PDGF and bFGF. |
| FND347 | Suture induced | FND | FND destroys not only blood but also lymphatic vessels, thereby promotes corneal high-risk graft survival. |
| PDT and verteporfin348 | Suture induced | PDT after I.V. injection of verteporfin |
Corneal PDT after i.v. verteporfin injection time-dependently regresses mature corneal BV and LV and promotes allograft survival after subsequent high-risk corneal transplantation. |
| UVA crosslinking and riboflavin308 | Suture induced | Topical riboflavin and then UVA light exposure | Corneal crosslinking with UVA light and riboflavin regressed both preexisting blood and lymphatic vessels significantly via induction of apoptosis in vascular endothelial cells. In addition, macrophages and CD45+ cell counts were significantly reduced. |
- ref = reference number, S.C. =subconjunctival, EC = endothelial cell, I.P. = intraperitoneal, I.V. = intravenous, BIGH3 = TGF-β1-inducible gene-h3, SDF = stromal-cell derived factor, LHT7 = Low-molecular-weight heparin (LMWH)–taurocholate derivative, HGF= hepatocyte growth factor, FND= fine-needle diathermy, PDT= photodynamic therapy, UVA= ultraviolet light A.
*
Increases CNV in early stages and decreases in later stages.