Figure 4.

CR2-fH rescues ultrastructural changes in RPE/BrM/CC complex in mice following cigarette exposure. Electron micrographs of the retinal pigment epithelium/Bruch's membrane/choriocapillaris complex (RPE/BrM/CC) obtained from age-matched mice after 6 months of cigarette smoke exposure (CSE) or room air followed by 3 months of treatment with PBS (smoke + PBS), CR2-fH (smoke + alternative complement pathway inhibitor, CR2-fH), or 3 additional months of room air (control, never smokers) were compared, providing an RPE/BrM/CC overview (A–C), or focusing on mitochondria (D–F) and BrM (G–I). In an animal raised in room air (control, never smoker), BrM exhibits an organized pentalaminar structure consisting of RPE basement membrane, inner collagenous layer, middle elastic layer, outer collagenous layer, and choriocapillaris basement membrane, and the choriocapillaris endothelium has fenestrations (arrowheads) along the entire membrane (A, G). (B, H) The RPE/BrM/CC in a mouse following CSE (smoke + PBS) exhibits pathologic changes. Bruch's membrane is disorganized, no longer showing a pentalaminar structure, and large deposits (asterisks) are present in the outer collagen layer (OCL). Notably, there is significant fenestration loss and/or endothelial cell thickening adjacent to OCL deposits. (C, I) The RPE/BrM/CC appears normal in mice treated with CR2-fH following CSE (smoke + CR2-fH). The morphologic features of mitochondria shown in mice exposed to smoke mitochondria have degraded outer membranes and disorganized cristae (E), but normal appearance in never smokers (D) and mice treated with CR2-fH following CSE (F).