Response of Retinal Connexin43 to Optic Nerve Injury

PURPOSE: To characterize the spatial and temporal expression of Connexin43 (Cx43) after partial optic nerve transection and evaluate its relationship to retinal ganglion cell (RGC) loss and retinal glial response. METHODS: Partial, unilateral, superior optic nerve transection was performed in 150 Wistar rats. The retinas were evaluated at 8 and 24 hours and 3, 7, 14, 28, and 56 days after injury. Immunohistochemical analysis identified changes in several markers including Cx43 immunoreactivity (ir), RGC counts (Brn3a), and retinal astrocytes (GFAP). RESULTS: After injury, superior retinal Cx43-ir peaked at 3 days (192.1% of control; P = 0.0002) and 28 days (212.1% of control; P < 0.0001) and troughed at 14 days (73.8% of control; P = 0.0028) and 56 days (72.5% of control; P = 0.0232). Inferior retinal Cx43-ir was elevated at only 28 days (127.4% increase; P = 0.0481). Superior RGC loss began at 3 days (84.0% of control; P = 0.0454) and continued to decline by 56 days (18.8% of control; P < 0.0001). Inferior RGC loss began at 28 days (73.4% of control; P = 0.0021). An increase in GFAP-ir occurred in the superior retina from day 3 (153.7% of control; P = 0.0017) and from day 28 (186.7% of control; P = 0.0013) in the inferior retina, persisting in both the superior and inferior retina to 56 days (P = 0.0027). CONCLUSIONS: A biphasic upregulation of retinal Cx43 protein occurs in the superior retina with peaks at 3 and 28 days after injury, but at only 28 days in the inferior retina. There is an associated loss of RGCs and a retinal astrocytic inflammatory response.