Histopathological features of mouse and human polypoidal choroidal vasculopathy (PCV) lesions. A–F: Representative indocyanine green angiography images of small (red arrow; A) and large (red arrow; B) PCV lesions that were isolated from a 9-month–old Tg44 for histopathology analysis (Richardson stain; C–F). C and E: Small lesions. D and F: Large lesions. G: Wild-type control. C–E: Dilated thin-wall vessels (black dashed ovals; C and E) with broken vessel wall (red arrowheads; C and E) were present in small lesions, whereas hyalinized vessels with thick wall were present in both small and large lesions (red dashed circle; C–E). Yellow arrows indicated pigment epithelium detachments frequently observed near the dilated thin-wall vessels (C and E). Red arrows and black arrows indicate small and large vacuoles, respectively, in the small PCV lesion (C and E). Red arrows indicated severe and extensive retinal pigment epithelium (RPE) degeneration in large PCV lesions (D). Yellow arrows, black arrowhead, and orange arrowheads indicated macrophages, neutrophil, and monocytes, respectively (D). Red brackets indicated that the RPE layer and the tip of outer segment (OS) were disintegrated into a debris zone (D and F). Red arrows indicated large undigested OS phagosomes as a result of RPE degeneration (F). H and I: Immunopositive cells for macrophage markers F4/80 (yellow arrows; H) and CD68 (black arrows; I) were present in severe Tg44 and human PCV lesions, respectively. J–M: Transmission electron microscopic images showed the presence of mast cells (purple asterisks; J), platelets (blue asterisks; K), macrophages (red oval and red cap; L and M), and neutrophils (yellow oval; M) in severe PCV lesions of Tg44. L: Red arrowheads mark the crossing points in Bruch membrane (BM) of a macrophage en route to RPE. The red cap indicates another macrophage that was already invaded into the sub-RPE space in a severe PCV lesion. The red arrow and yellow arrow indicate degenerating endothelial cells and pericytes, respectively, in the large lesion. Scale bars: 100 μm (A and B); 10 μm (C, D, H, and I); 20 μm (E–G); 2 μm (J–M). Cho, choroid; IS, inner segment; ONL, outer nuclear layer.