Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114, USA.
Tulane University School of Medicine, Tulane Medical Center, New Orleans, LA 70112, USA.
Cells. 2023 Jun 30;12(13):1754. doi: 10.3390/cells12131754.
Retinal detachment (RD) is a neurodegenerative blinding disease caused by plethora of clinical conditions. RD is characterized by the physical separation of retina from the underlying retinal pigment epithelium (RPE), eventually leading to photoreceptor cell death, inflammation, and vision loss. Albeit the activation of complement plays a critical role in the pathogenesis of RD, the retinal cellular source for complement production remains elusive. Here, using C3 tdTomato reporter mice we show that retinal injury upregulates C3 expression, specifically in Müller cells. Activation of the complement cascade results in the generation of proinflammatory cleaved products, C3a and C5a, that bind C3aR and C5aR1, respectively. Our flow cytometry data show that retinal injury significantly upregulated C3aR and C5aR1 in microglia and resulted in the infiltration of peripheral immune cells. Loss of C3, C5, C3aR or C5aR1 reduced photoreceptor cell death and infiltration of microglia and peripheral immune cells into the sub-retinal space. These results indicate that C3/C3aR and C5/C5aR1 play a crucial role in eliciting photoreceptor degeneration and inflammatory responses in RD.
视网膜脱离（RD）是一种由多种临床病症引起的神经退行性致盲性疾病。RD 的特征是视网膜与底层视网膜色素上皮（RPE）的物理分离，最终导致光感受器细胞死亡、炎症和视力丧失。尽管补体的激活在 RD 的发病机制中起着关键作用，但补体产生的视网膜细胞来源仍不清楚。在这里，我们使用 C3 tdTomato 报告小鼠表明，视网膜损伤会特异性地上调 Müller 细胞中的 C3 表达。补体级联的激活导致产生促炎的裂解产物 C3a 和 C5a，它们分别与 C3aR 和 C5aR1 结合。我们的流式细胞术数据表明，视网膜损伤会显著上调小胶质细胞中的 C3aR 和 C5aR1，并导致外周免疫细胞浸润到视网膜下腔。C3、C5、C3aR 或 C5aR1 的缺失减少了光感受器细胞的死亡以及小胶质细胞和外周免疫细胞向视网膜下腔的浸润。这些结果表明，C3/C3aR 和 C5/C5aR1 在引发 RD 中的光感受器变性和炎症反应中起着至关重要的作用。
