A Chronic Ocular-Hypertensive Rat Model induced by Injection of the Sclerosant Agent Polidocanol in the Aqueous Humor Outflow Pathway

Int J Mol Sci. 2019 Jun 29;20(13):3209. doi: 10.3390/ijms20133209.

Abstract

Background: To induce a moderate chronic ocular hypertension (OHT) by injecting polidocanol, a foamed sclerosant drug, in the aqueous humor outflow pathway.

Methods: Intraocular pressure (IOP) was monitored for up to 6 months. Pattern and full-field electroretinogram (PERG and ERG) were recorded and retinal ganglion cells (RGC) and retinal nerve fiber layer (RNFL) thickness were assessed in vivo with optical coherence tomography (OCT) and ex vivo using Brn3a immunohistochemistry.

Results: In the first 3 weeks post-injection, a significant IOP elevation was observed in the treated eyes (18.47 ± 3.36 mmHg) when compared with the control fellow eyes (12.52 ± 2.84 mmHg) (p < 0.05). At 8 weeks, 65% (11/17) of intervention eyes had developed an IOP increase >25% over the baseline. PERG responses were seen to be significantly reduced in the hypertensive eyes (2.25 ± 0.24 µV) compared to control eyes (1.44 ± 0.19 µV) (p < 0.01) at week 3, whereas the ERG components (photoreceptor a-wave and bipolar cell b-wave) remained unaltered. By week 24, RNFL thinning and cell loss in the ganglion cell layer was first detected (2/13, 15.3%) as assessed by OCT and light microscopy.

Conclusions: This novel OHT rat model, with moderate levels of chronically elevated IOP, and abnormal PERG shows selective functional impairment of RGC.

Keywords: chronic ocular hypertension; optical coherence tomography; pattern and full-field electroretinogram; polidocanol injection; rat glaucoma model.

MeSH terms

  • Animals
  • Disease Models, Animal*
  • Glaucoma / etiology*
  • Glaucoma / metabolism
  • Glaucoma / pathology
  • Injections, Intraocular
  • Intraocular Pressure
  • Male
  • Polidocanol / toxicity*
  • Rats
  • Rats, Wistar
  • Sclerosing Solutions / toxicity*
  • Transcription Factor Brn-3A / metabolism

Substances

  • Pou4f1 protein, mouse
  • Sclerosing Solutions
  • Transcription Factor Brn-3A
  • Polidocanol