Eye Drop Instillation of the Rac1 Modulator CNF1 Attenuates Retinal Gliosis and Ameliorates Visual Performance in a Rat Model of Hypertensive Retinopathy

Neuroscience. 2019 Jul 15:411:119-129. doi: 10.1016/j.neuroscience.2019.05.021. Epub 2019 May 23.

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.

Keywords: Rac1 protein; cytotoxic necrotizing factor 1; gliosis; hypertensive retinopathy; ophthalmic solutions; spontaneously hypertensive rats.

MeSH terms

  • Animals
  • Bacterial Toxins / administration & dosage
  • Bacterial Toxins / therapeutic use*
  • Disease Models, Animal
  • Escherichia coli Proteins / administration & dosage
  • Escherichia coli Proteins / therapeutic use*
  • Gliosis / drug therapy*
  • Gliosis / physiopathology
  • Hypertensive Retinopathy / drug therapy*
  • Hypertensive Retinopathy / physiopathology
  • Male
  • Ophthalmic Solutions
  • Rats
  • Rats, Inbred SHR
  • Retina / drug effects*
  • Retina / physiopathology
  • Vision, Ocular / drug effects*

Substances

  • Bacterial Toxins
  • Escherichia coli Proteins
  • Ophthalmic Solutions
  • cytotoxic necrotizing factor type 1