Transcorneal electrical stimulation prevents secondary retinal ganglion cell death after acute ocular hypertensive injury through modulation of microglia-mediated local inflammatory response

Abstract

PURPOSE: To investigate neuroprotective effect of transcorneal electrical stimulation (TcES) on retinal ganglion cells (RGC) after acute ocular hypertension related retinal injury in gerbils. METHODS: The right eye of each gerbil was used for experiments. Acue ocular hypertensive injury was induced via intracameral infusion of basic salt solution. Intraocular pressure (IOP) was adjusted by changing the bottle height position. For all gerbis, right eye IOP was elevated to 85 mmHg for 1 h. In the treatment group, TcES was applied to the surgical eye immediately and then twice weekly for a total of 1 month. In the control group, sham TcES was given to the surgical eye during the same time points. Retinal function was assessed and compared between groups using a full field flash electroretinogram and a light/dark transition box test. For histological analysis, the number of RGCs, astrocytes and microglial cells were counted by immunofluorescence staining after the gerbils were sacrificed on day 7 and day 28. Real time PCR and western blot analysis were conducted to compare expression of IL-10, IL-6, Cox-2, TNF-α and NFκB phorsphorylation between groups. RESULTS: TcES treated eyes had significantly higher RGC survival at 1 month compared to controls. This was associated with improved RGC function and vision-related behaviour. Furthermore TcES treated eyes were shown to have increased IL-10 expression, with a corresponding reduction in IL-6 and COX-2 expression as well as reduction in NF-kB phosphorylation. This was associated with a suppression in microglial cell activation in TcES treated eyes. CONCLUSIONS: Early treatment with TcES in gerbils protected the RGCs from damage and preserved retinal function in acute ocular hypertensive injury through modulation of the microglial-cell activated local inflammatory response.