Neuroinflammation is involved in the death of retinal ganglion cells (RGCs) after optic nerve injury. The purpose of this study was to determine whether systemic simvastatin can suppress neuroinflammation in the optic nerve and rescue RGCs after the optic nerve is crushed. Simvastatin or its vehicle was given through an osmotic minipump beginning one week prior to the crushing. Immunohistochemistry and real-time PCR were used to determine the degree of neuroinflammation on day 3 after the crushing. The density of RGCs was determined in Tuj-1 stained retinal flat mounts on day 7. The effect of simvastain on the TNF-α-induced NF-κB activation was determined in cultured optic nerve astrocytes. On day 3, CD68-positive cells, most likely microglia/macrophages, were accumulated at the crushed site. Phosphorylated NF-κB was detected in some astrocytes at the border of the lesion where the immunoreactivity to MCP-1 was intensified. There was an increase in the mRNA levels of the CD68 (11.4-fold), MCP-1 (22.6-fold), ET-1 (2.3-fold), GFAP (1.6-fold), TNF-α (7.0-fold), and iNOS (14.8-fold) genes on day 3. Systemic simvastatin significantly reduced these changes. The mean ± SD number of RGCs was 1816.3±232.6/mm2 (n = 6) in the sham controls which was significantly reduced to 831.4±202.5/mm2 (n = 9) on day 7 after the optic nerve was crushed. This reduction was significantly suppressed to 1169.2±201.3/mm2 (P = 0.01, Scheffe; n = 9) after systemic simvastatin. Simvastatin (1.0 µM) significantly reduced the TNF-α-induced NF-κB activation in cultured optic nerve astrocytes. We conclude that systemic simvastatin can reduce the death of RGCs induced by crushing the optic nerve possibly by suppressing astroglial NF-κB activation.

The observed Müller cell swelling is mediated by VEGF and AQP4.

Background: Branch retinal vein occlusion (BRVO) commonly occurs at the arteriovenous crossing in the unilateral eye, and cardiovascular diseases can be risk factors of BRVO. However, the pathomechanism leading to BRVO is not yet clear. In addition to mechanical compression, the vein might locally constrict due to an altered biochemical environment, such as an increase in the concentration of endothelin-1 (ET-1). We evaluated changes in ET-1 following injection of intravitreal bevacizumab (IVB), which is the anti-vascular endothelial growth factor (VEGF) agent with the longest serum half-life, to determine the effect on BRVO-related macular edema.

Purpose: To investigate the effect of a selective aquaporin 4 (AQP4) inhibitor, 2-(nicotinamide)-1,3,4-thiadiazole (TGN-020), on the expression of vascular endothelial growth factor (VEGF) and reactive oxygen species (ROS) production, as well as on the retinal edema in diabetic retina. Methods: Intravitreal injections of bevacizumab, TGN-020, or phosphate-buffered saline (PBS) were performed on streptozotocin-induced diabetic rats. Retinal sections were immunostained for anti-glial fibrillary acidic protein (GFAP), anti-AQP4, and anti-VEGF. Protein levels of VEGF from collected retinas were determined by Western blot analysis. In addition, retinal vascular leakage of Evans Blue was observed in the flat-mounted retina from the diabetic rats in the presence or absence of TGN-020. Volumetric changes of rat retinal Müller cells (TR-MUL5; transgenic rat Müller cells) and intracellular levels of ROS were determined using flow cytometry analysis of ethidium fluorescence in the presence or absence of TGN-020 or bevacizumab under physiological and high glucose conditions. Results: In the diabetic retina, the immunoreactivity and protein levels of VEGF were suppressed by TGN-020. AQP4 immunoreactivity was higher than in the control retinas and the expressions of AQP4 were co-localized with GFAP. Similarly to VEGF, AQP4 and GFAP were also suppressed by TGN-020. In the Evans Blue assay, TGN-020 decreased leakage in the diabetic retinas. In the cultured Müller cells, the increase in cell volumes and intracellular ROS production under high glucose condition were suppressed by exposure to TGN-020 as much as by exposure to bevacizumab. Conclusion: TGN-020 may have an inhibitory effect on diabetic retinal edema.

BackgroundWe report a case of traumatic retinal detachment in an eye with severe corneal opacity that was successfully treated using 23 gauge (G) transconjunctival vitrectomy assisted by endoscope and a wide-angle viewing system.Case presentationA 22-year-old Japanese man was referred to our hospital with the suspicion of traumatic retinal detachment of the right eye, 1 month after an open globe eye injury due to fireworks. At the time of his first visit, his best-corrected visual acuity was hand motion in the right eye. A 23 G three port pars plana vitrectomy was conducted in combination with ophthalmic endoscope and a wide-angle viewing system. Endoscopy revealed a retinal detachment in the inferior quadrant with tiny retinal breaks. Primary reattachment of the retina was achieved by tamponade of SF6 gas. Five months after the vitrectomy, penetrating keratoplasty was performed and visual acuity recovered to 0.02. Optical coherent tomography revealed thinning of the retina, which might be the cause of the remaining poor vision.Conclusion23 G vitrectomy assisted by combined endoscopy and a wide-angle viewing system could be advantageous in managing visualization constraints due to penetrating trauma.