Telmisartan Reduces Axon Degeneration in Mice With Experimental Glaucoma

Invest Ophthalmol Vis Sci. 2020 May 11;61(5):51. doi: 10.1167/iovs.61.5.51.

Abstract

Purpose: The purpose of this study was to determine if treatment with telmisartan, an angiotensin II type 1 receptor blocker (ARB), protects against retinal ganglion cell (RGC) degeneration in a mouse glaucoma model with induced elevation of intraocular pressure (IOP).

Methods: IOP elevation was induced by injection of polystyrene microbeads into the anterior chamber of the right eye of 3-month-old C57BL/6J mice, with the left eye serving as contralateral control. Starting the day of microbead injection, mice were maintained on solid food pellets with or without incorporated telmisartan. IOP was measured by Tono Lab tonometry prior to and weekly after microbead injection. Twelve weeks postinjection, mice were euthanized to obtain optic nerves for analysis of RGC axons. The total numbers of optic nerve axons were determined manually and automatedly using AxonJ. Degenerating axons were counted manually.

Results: IOP elevation induced by microbead injection was similar in magnitude and duration in vehicle and telmisartan-fed mice, although IOP was reduced 5.8% in uninjected mice treated with telmisartan (P = 0.0027). Axon loss determined by manual and automated methods was greater in vehicle compared to telmisartan-treated mice (manual: 9.5% vs. 1.8%, P = 0.044; automated: 14.2% vs. 2.9%, P = 0.0375). An increase in the percent of axons undergoing degeneration was observed in nerves from microbead-injected eyes that was greater in vehicle-treated compared to telmisartan-treated mice (49.0% vs. -0.58%, P = 0.0019).

Conclusions: Elevation of IOP by microbead injection led to loss of RGC axons in vehicle-treated mice that was largely prevented by telmisartan treatment, suggesting a neuroprotective effect of telmisartan.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II Type 1 Receptor Blockers / pharmacology*
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Animals
  • Axons / drug effects*
  • Axons / pathology*
  • Disease Models, Animal
  • Female
  • Glaucoma / drug therapy*
  • Glaucoma / pathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Retinal Ganglion Cells / drug effects*
  • Retinal Ganglion Cells / pathology*
  • Telmisartan / pharmacology*
  • Telmisartan / therapeutic use*

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Telmisartan