Abstract
Purpose :
Angiotensin II type 1 receptor blockers (ARBs), commonly used to treat systemic hypertension, interfere with transforming growth factor beta (TGFβ) signaling, which is believed to play an important role in glaucoma pathogenesis. We have previously shown that oral administration of telmisartan reduces TGFβ signaling in the retinal ganglion cell layer and lowers IOP in normal mice. The purpose of this study is to investigate the neuroprotective capability of telmisartan as a potential treatment for glaucoma.
Methods :
Experimental glaucoma was induced unilaterally in 3-month-old C57BL/6J mice by anterior chamber injection of polystyrene microbeads, inducing chronic elevation of IOP. Telmisartan or vehicle control were administered orally in the chow on the day of microbead injection and maintained ad libitum for 11 weeks. Before and every 7 days after microbead injection, IOP was measured by TonoLab rebound tonometry. Eleven weeks post-microbead injection, mice were killed and eyes were processed for optic nerve axon counting (manually and using AxonJ software) and pSmad2 (a marker of TGFβ signaling) immunohistochemistry.
Results :
In vehicle control mice, there was a significant reduction in the number of axons in microbead-injected eyes compared to contralateral control eyes (p = 0.026, n = 13). However, there was no difference in axon count in the telmisartan-treated group (p = 0.22, n = 17). Telmisartan-treated mice also had significantly reduced integrated IOP over the 11 weeks compared to mice fed vehicle diet (p = 0.0008). Expression of pSmad2 tended to be lower in the retinal ganglion cell layer following telmisartan treatment.
Conclusions :
Chronic elevation of IOP by unilateral injection of microbeads in the anterior chamber of mice lead to a significant reduction in axons, representing glaucomatous optic neuropathy. Telmisartan prevented axon loss, reduced IOP, and tended to reduce TGFβ signaling after microbead injection, suggesting a neuroprotective effect of this ARB for glaucoma in mice.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.