Abstract
Purpose:
Retinal vein occlusion (RVO) is an important cause of blindness because of the subsequent microvascular remodelling that may lead to a variable combination of capillary non-perfusion and macular edema. To date, the inflammatory processes that accompany BRVO and its role in the microvascular remodelling have received little attention. Here, we analyzed the involvement of inflammation in a model of laser-induced BRVO in mice.
Methods:
A complete and permanent occlusion of a retinal vein of C57Bl/6J Rj mice was obtained using 534nm laser. We followed in vivo the development of tissue changes by funduscopy, scanning laser ophthalmoscopy and optical coherence tomography. At different time points after RVO, animals were sacrificed and the expression of various genes were analyzed by real-time RT-PCR. Iba1 immunostaining was performed on the whole retina at 3 and 7 days after RVO to evaluate macrophage/microglia responses. To quantify cell proliferation, mice were intraperitoneally injected with the nucleotide analog EdU and killed at 3d and 7d after RVO.
Results:
Permanent occlusion of a retinal vein was obtained in all treated eyes with minimal damage to surrounding tissue. Subsequently, dilation of the affected vein was observed. Few retinal hemorrhages were observed at 24h which slightly increased at day 3. Retinal mRNA expression of the chemokine CCL2 significantly increased 4h after RVO. The macrophage/microglia markers F4/80 and cd11b increased at 3 days. Macrophage/microglia recruitment was confirmed at 3d by increased Iba1 positive cells throughout the area of the occluded vein and persisted at 7d after RVO. Iba1-positive perivascular macrophages were also more numerous around occluded veins up to the periphery than intact veins in the same eye or in control eyes. The macrophage/microglia response was still increased at 7d after RVO but at lower levels. Seven days after RVO, proliferation occurred mainly in endothelial cells of capillaries upstream of the occluded vein.
Conclusions:
Our data shows that BRVO induces CCL2 expression and perivascular and retinal macrophage recruitement concomittantly with retinal hemorraghe and endothelial cell proliferation distal to the laser site. The BRVO mouse model will allow us to study the role of inflammatory processes in vascular leakage and endothelial cell proliferation.
Keywords: 749 vascular occlusion/vascular occlusive disease •
557 inflammation •
688 retina