Morphological features of tip cells in corneal, retinal, and cho-roidal neovascularization in mice

In the current research, we used the techniques of DLL4/IB4/CD31/LYVE-1 im-munofluorescence (IF) staining and confocal microscopy to view the morphological features of tip cells in models of corneal, retinal, and choroidal neovascularization in mice. We confirmed that DLL4-positive tip cells have distinct morphological features. Under the conditions of normal angiogenesis in the retina on day 5 after birth, classical DLL4 tip cells with filopodial extensions were observed. Pathological models, in turn, showed special morphological patterns in corneal neovascularization (CoNV), elongated curved filopodia-like structures were characteristic; in retinal neovascularization (RNV), branched tip cells were observed; in choroidal neovascularization (CNV), disordered grouped structures were observed. These observations reveal the tip-cell morphological heterogeneity in the variety of vascular microenvironments. The comparison provides new insights into the endothelial cell behavior in the process of normal and pathological angiogenesis, which allows one to gain further insights into the mechanisms of vascular patterning in ocular neovascular diseases. The observed morphological tip-cell features can act as potential markers for the development of targeted therapeutic interventions against abnormal vessel growth.