CORRELATIVE INCREASES IN ASTROCYTE, MICROGLIA, AND C1Q IN A MURINE MODEL OF ACUTE GLAUCOMATOUS INJURY

Glaucoma is an injury to cells of the eye indicated by pressure within the eye which can lead to eventual blindness. Microglial cells are a special type of cell within the central nervous system (CNS) that cleans up cellular damage. Astrocytes are another specialized cell which plays a supportive role important for CNS function. C1q is a part of the immune system usually reserved for clearance of bacteria from the body, but has been recently demonstrated to serve other roles. Microglia and C1q have been implicated in mediating retinal damage in mouse models mimicking glaucoma. This study was conducted to investigate if C1q and either microglia or astrocytes, or both, could be involved in brain damage caused by a simulated glaucoma injury. Purpose (a): Glaucoma is a leading cause of blindness worldwide. Recent studies of glaucomatous retinal injury have observed a correlation of upregulated C1q and increased microglial activity. Using the optic nerve crush (ONC) model of glaucoma, we are investigating whether there is an injurious response involving C1q, microglia, and astrocytes within the superior colliculus (SC), the visual center of the mouse brain. Methods (b): Glaucomatous injury was simulated in mice using ONC of the left eye, while leaving the right eye intact. Brain tissue was harvested at 0, 7, 14, and 28 days post-injury, fixed overnight in 4% paraformaldehyde, and paraffin embedded. Following paraffin removal and antigen recovery, immunohistochemistry was performed to label astrocytes (GFAP), microglia (IBA1), and C1q in the SC. Results (c): Beginning 7 days post-injury, there was an increase in astrocytes, microglia, and C1q, with microglia assuming an activated morphology. Astrocytes and C1q remained elevated through 28 days post-injury, with a gradual reduction in microglial density. These results were observed only within the SC contralateral to the injured nerve, the main target of the retinal ganglion cell (RGC) axons from the ONC eye. Increased C1q and astrocyte activity was not observed in the ipsilateral hemisphere; however, there was a slight increase in microglial density. Conclusions (d): Our data support a similar response in the retina and SC of upregulated C1q, resulting from glaucomatous injury. Microglia and astrocytes also appear to be involved in the acute injury phase. Previous studies of retinal glaucomatous injury have shown that early reduction of C1q is protective. Future studies using a C1q-deficient mouse model might also show protective function against SC glaucomatous injury.