Retinal Injury Activates Complement Expression in Müller Cells Leading to Neuroinflammation and Photoreceptor Cell Death.

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.

Bilateral Coronal Synostosis and Mega Cisterna Magna: A Case Report.

Craniosynostosis is often associated with raised intracranial pressure (ICP), especially when multiple sutures are involved. In this report, we discuss an unusual association in a patient with craniosynostosis. We report a case of a two-year-old Caucasian male with bilateral coronal synostosis (BCS) who was found to have a concomitant mega cisterna magna (MCM). Although counterintuitive, even in the presence of craniosynostosis, patients with this finding can also have intracranial CSF fluid collections such as the MCM reported here. We hope this report will enhance our understanding of some similar cases that are equivocal regarding raised ICP.