Retinal macroglial activation over time in an experimental glaucoma model

Abstract

AbstractPurpose: The aim of this study was to analyse the effects of unilateral laser‐induced ocular hypertension (OHT) on macroglia in OHT and contralateral eyes at different time points after laser treatment (1, 3, 5, 8 and 15 days).Methods: Two groups of albino Swiss mice: naïve group (n = 6) and OHT group (n = 30, six animals for each time study group). In the OHT group, OHT was induced by laser photocoagulation of the limbal and episcleral veins of the left eyes. Retinal whole‐mounts were used to visualize the astroglial plexus throughout the retinal extension, analysing the GFAP‐labelled retinal area (GFAP‐RA), the intensity of GFAP labeling (GFAP‐IRI), and the intensity of MHC‐II expression (MHC‐II‐IRI) in both OHT eyes and normotensive contralateral eyes compared to naïve eyes.Results: In OHT and contralateral eyes, with respect to naïve eyes, at all the time points, we found the following: (i) astrocytes with thicker somas and more secondary processes, mainly in the intermediate (IR) and peripheral retina (PR); (ii) astrocytes with low GFAP‐IRI and only primary processes near the optic disc (OD); (iii) increased total GFAP‐RA, which was higher at 3 and 5 days, except for at 15 days; (iv) increased GFAP‐IRI in the IR and especially in the PR: (v) decreased GFAP‐IRI near the OD, mainly at 1 and 5 days; (vi) a significant increase in MHC‐II‐IRI, which was higher in the IR and PR; and (vii) GFAP+ and MHC‐II+ immunolabelling in the Müller glia.Conclusions: Increased IOP leads, both in OHT eyes and in their normotensive contralateral eye, to macroglial activation, demonstrated both by morphologic changes and by the overexpression of GFAP and MHC‐II. The main signs of activation were observed mainly in the IR and PR, being more intense at 3 and 5 days after induction. However, in the OD, astrocytes showed low expression of GFAP and MHC‐II. The bilateral macroglial activation observed in this study would be triggered by the immune response associated with neuroinflammation.