|
| Growth factors | Utilized
pathway | Cellular target | Cellular effects | Corneal effects | Tear level | Serum level | References |
|
| EGF | EGFR/erbB1/HER1, erbB2/HER2/neu, erbB3/HER3, erbB4/HER4 | Corneal epithelial cells (limbal region) | It increases epithelial migration and proliferation, inhibits corneal epithelial terminal differentiation, and upregulates activations of B4 integrins. | It stimulates epithelial wound closure accelerating the healing time. | 2053 ± 312.4 pg/mL |
199.74/±64.74 pg/mL | [16] |
|
| TGF-α | EGFR/erbB1/HER1, erbB2/HER2/neu, erbB3/HER3, erbB4/HER4 | Corneal epithelial cells | It increases epithelial migration and proliferation and inhibits the expression of keratin K3. | It leads edge extension in epithelial sheet migration during eyelid closure. | 84 ± 19 pg/mL | 120 to 207 pg/mL | [16, 20, 21] |
|
| KGF | Ras-MAPK, PI3K/p70S6 | Corneal epithelial cells | It increases epithelial cell proliferation protecting them from hypoxia. | It stimulates epithelial wound closure accelerating the healing time in the limbus zone. | Not provided | 10.63 ± 4.98 pg/mL | [56] |
|
| HGF | c-Met, Ras-MAPK, PI3K/AKT, p70S6K, EGFR | Corneal epithelial cells, fibroblasts | It increases epithelial cell migration and motility and proliferation and inhibits apoptosis. | It stimulates epithelial wound closure. | 200 pgmL−1 | 573.9 ± 142.8 pgmL−1 | [18, 57] |
|
| IGF-1 | PI3K/AKT | Corneal epithelial cells, fibroblasts | It increases epithelial cell proliferation, inhibits apoptosis, increases chemotaxis, and increases the expression of connexin 43 in corneal fibroblasts. | It stimulates epithelial wound closure improving gap-junctions. | Not provided | 173.5 ng/mL | [6] |
|
TGF
β1/β2 | TGF β-RI
TGF β-RII | Corneal epithelial cells, fibroblasts (limbal and central region) | It inhibits epithelial cells proliferation, increases keratocyte proliferation, and promotes myofibroblast differentiation. | It promotes scar formations, delays reepithelialization, and inhibits angiogenesis. | 10 ng/mL | 50 ng/mL | [24] |
|
| PDGF | PDGF-R | Endothelial cell, fibroblasts, epithelial cells | It increases endothelial cell proliferation, enhances fibroblast migration, and increases chemotaxis of epithelial cells. | It stimulates epithelial wound closure. | 95–1330 ng/L | 1.70 ng/mL | [22] |
|
| FGF-2 | FGF-R, heparan sulfate proteoglycans, RTKs | Corneal epithelial cells, fibroblasts (Bowman’s and Descemet’s membrane) | It increases epithelial, endothelial, and stromal cell proliferation. | It stimulates epithelial wound closure and improves gap-junctions. | Not provided | 8.3 ± 1.75 pg/mL | [13] |
|
| NGF | TRKA-R | Corneal epithelial cells, endothelial cells, fibroblasts | It increases epithelial cell proliferation and differentiation. | It stimulates epithelial wound closure, improves nerve regrowth, and induces inflammation and vascularization. | 8.3 +/− 4.7 ng/ml | 18.5 +/− 6.1 ng/mL | [19, 62, 63] |
|
