Eye Drop Instillation of the Rac1 Modulator CNF1 Attenuates Retinal Gliosis and Ameliorates Visual Performance in a Rat Model of Hypertensive Retinopathy. (15th July 2019)

• Record Type: Journal Article
• Authors: Matteucci, Andrea; Ricceri, Laura; Fabbri, Alessia; Fortuna, Andrea; Travaglione, Sara; Guidotti, Marco; Martinelli, Andrea; Villa, Marika; Pricci, Flavia; Maroccia, Zaira; Campana, Gabriele; Malchiodi-Albedi, Fiorella; Fiorentini, Carla; Loizzo, Stefano
• Is Part Of: Neuroscience. Volume 411(2019)
• Page Start: 119
• Page End: 129
• Publication Date: 2019-07-15
• Subjects: CNS central nervous system -- GFAP glial fibrillary acidic protein -- CNF1 cytotoxic necrotizing factor 1 -- SHRs spontaneously hypertensive rats -- VEPs visual evoked potentials -- ERK1/2 extracellular signal-regulated kinase 1/2 -- pERK1/2 phosphorylated ERK1/2 -- EEGs electroencephalographies -- WB western blot -- PAGE polyacrylamide gel electrophoresis -- HP highpass -- LP lowpass -- TBS-T tris-buffered saline-tween -- IPL inner plexiform layer -- PBS phosphate buffered saline; cytotoxic necrotizing factor 1 -- hypertensive retinopathy -- Rac1 protein -- gliosis -- ophthalmic solutions -- spontaneously hypertensive rats; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2019.05.021
• Languages: English
• ISSNs: 0306-4522

Abstract

Abstract: In hypertensive retinopathy, the retinal damage due to high blood pressure is accompanied by increased expression of Glial Fibrillary Acidic Protein (GFAP), which indicates a role of neuroinflammatory processes in such a retinopathy. Proteins belonging to the Rho GTPase family, particularly Rac1, are involved in the activation of Müller glia and in the progression of photoreceptor degeneration, and may thus represent a novel candidate for therapeutic intervention following central nervous system inflammation. In this paper, we have observed that topical administration as eye drops of Cytotoxic Necrotizing Factor 1 (CNF1), a Rho GTPase modulator, surprisingly improves electrophysiological and behavioral visual performances in aged spontaneously hypertensive rats. Furthermore, such functional improvement is accompanied by a reduction of Rac1 activity and retinal GFAP expression. Our results suggest that Rac1 inhibition through CNF1 topical administration may represent a new strategy to target retinal gliosis. Highlights: Rac1 may represent a novel candidate for therapeutic intervention following retinopathy. CNF1 improves electrophysiological and behavioral visual performances in aged spontaneously hypertensive rats. CNF1 topical administration, through Rac1 inhibition, may constitute a new therapeutic approach to target retinal gliosis.