(A and E) At P12, vascular obliteration was similar in S1p2^+/+ (34.2% ± 2.14%; n = 4), S1p2^+/– (31.2% ± 0.9%; n = 3), and S1p2^–/– whole mount retinas (31.9% ± 3.6%; n = 2, *P = 0.37) stained for GS-lectin. (B and E) At P14, vascular obliteration was also similar in S1p2^+/– (34.19% ± 0.74%; n = 3) and S1p2^–/– (32.49% ± 2.4%; n = 6; **P = 0.1) retinas. (C and E) At P16, S1p2^+/– retinas developed abnormal buds (arrowhead), and the capillary-free area was 16.6% ± 1.9% (n = 3); S1p2^–/– retinas had improved vascular morphology (arrow) and reduced capillary-free area (8.6% ± 1.7%; n = 7; ***P < 0.001). (D and E) At P17, S1p2^+/+ (n = 2) and S1p2^+/– (n = 11) retinas displayed 13.5% ± 1.3% and 13.15% ± 1.8% vascular obliteration, respectively, and increased neovascularization (arrowhead, inset; scale bar: 100 μm); S1p2^–/– retinas (n = 9) showed significantly decreased capillary-free area (2.6% ± 2.9%; ^#P < 0.0001). Scale bar: 200 μm. (F and G) At P17, PAS and hematoxylin–stained cross section of S1p2^+/+ retinas with evident formation of vascular tufts (VT). (H) At P15, the mean number of neovascular nuclei/section for S1p2^+/+ and S1p2^+/– was 22.5 ± 3.7 (n = 2) and 19.58 ± 2.43 (n = 4), respectively. S1p2^–/– retinas showed a decreased number, 11.27 ± 2.16 (n = 4; *P < 0.0025). At P17, the mean number of neovascular nuclei/section for S1p2^+/+ and S1p2^+/– retinas was 37.6 ± 7.03 (n = 3) and 34.528 ± 6.2 (n = 5), respectively. S1p2^–/– retinas displayed a reduced number, 19.62 ± 2.2 (n = 6; ^#P < 0.001). Scale bar: 100 μm (F) and 10 μm (G). Values represent mean ± SD. HT, heterozygous.