Destrin−/− mice, corn1 mice | Pro-angiogenic VEGFR-3 signaling, deficient in sVEGFR-1 | ✓ | ✓ | Starts at 20 days | Rescue by VEGFR-3 neutralization or application of sVEGFR-1 | Spontaneous corneal HA and LA, differentially regulated by genetic background, different time kinetics of HA and LA | 10, 77, 78, 94, 96, 97 |
TSP-1−/− mice | Loss of antiangiogenic signaling of CD36+ macrophages | ✗ | ✓ | Starts at 6 mo | Rescued by wild-type bone marrow cells | TSP-1 inhibits VEGF-C release and LA by binding to its receptor CD36 on monocytes | 13 |
CD36−/− mice | Loss of TSP-1 – CD36 interaction | ✓ | ✓ | Late onset (approximately 1 y) | None | Upregulation of VEGF-A is observed when CD36 is knocked out | 13, 84 |
KLEIP/KLHL20−/− mice | Proangiogenic miR-204 – Ang-1 pathway | ✓ | ✓ | Median time 8 wk | Anti-VEGF therapy not effective | Includes macrophage infiltration and spontaneous corneal NV, accelerated by superficial abrasion | 24, 62 |
LRIG1−/− mice | LRIG1 acts as a negative regulator of STAT3 | ✓ | ✗ | Median time 18 mo | STAT3 inhibition by STA21 or wild-type bone marrow cells rescue phenotype | Spontaneous, can be induced by injury | 85 |
K5.Stat3C mice | Proinflammatory STAT3 signaling | ✓ | ✗ | Similar to LRIG1−/− | None | Similar phenotype to LRIG1 deficient mice | 85 |
Jam-A−/− mice | VEGF expression and TGF-β activation | ✓ | ✗ | Starting early but low prevalence | Inhibition of HA by DC101 (anti VEGFR-2 antibody) | Spontaneous, can be accelerated by injury, approximately 50% prevalence at 6–12 mo | 86, 87 |
ADAMTS9+/− mice | ADAMTS9 is an antiangiogenic metalloprotease | ✓ | ✗ | Median time approximately 6 wk | None | 80% prevalence in heterozygous mice (only in C57BL/6 strain). Null mice are not viable | 128 |
Le-Cre;Cited2loxP/loxP | Presumably via Pax6 and Klf4 | ✓ | ✗ | 8 mo | None | High penetrance | 129 |
MxCre;RBPf/f | Downstream of Notch receptor | ✓ | ✗ | Approximately 2 mo | None | Spontaneous NV affects various ocular and extraocular tissues (cornea, retina, liver, lung) | 130 |
Pax6 overexpression using the Aldh3a1 promoter | Chi3l4, Flt-1, Wif1 | ✓ | ✗ | Approximately 6–12 wk | None | Up to 69% prevalence, associated with corneal inflammation | 88 |
Pax6+/− mice | Presumably due to epithelial defects; sVEGFR-1 deficiency | ✓ | ✗ | Early phenotype starting at 2 weeks | Rescued by application of sVEGFR-1 | Incomplete prevalence (different prevalence reports), several anterior eye defects including corneal NV | 10, 89, 90 |
Global FoxC1−/− mice and neural-crest specific FoxC1−/− | Via VEGF – VEGFR-2 signaling | ✓ | ✓ | Detectable at 15 days after birth | Inhibition of HA by blocking VEGFR-2 signaling | Linked to disrupted epithelial architecture; FoxC1−/− mice show spontaneous corneal NV, FoxC1± mice show increased corneal NV upon injury | 15 |
LeCre;VEGFR-2loxP/loxP | Lack of sVEGFR-2 | ✗ | ✓ | At birth | Inhibition of LA by blocking VEGFR-3 signaling | 100% prevalence in N = 30 mice | 14 |
pCre;VEGFR-1loxP/loxP | Lack of sVEGFR-1 | ✓ | ✗ | Starting 2 d after pCre injection | None | Fully vascularized at 14 days, high prevalence in n = 10 mice | 10 |
C57BL/6 mice | Unknown | ✗ | ✓ | P6–P14 | None | During development, the mouse cornea presents lymphatic vessel sprouting and regression | 41 |
Nude mice, nu/nu, and hairless mutant mouse strain, SKH1;hr/hr | Proangiogenic factors probably coming from the epithelium | ✓ | ✓ | 6–12 wk old mice | None | Spontaneous corneal NV associated with absence of hair in 2 different genetic mouse models | 76, 92 |
Heme oxygenase (HO)-2 | MMP-2 | ✓ | ✗ | Not applicable | shRNA injection | Local knockdown, not transgenic. Negative regulation of HA | 131 |