Azithromycin and Sildenafil May Have Protective Effects on Retinal Ganglion Cells via Different Pathways: Study in a Rodent Microbead Model

Tal Corina Sela, Alon Zahavi, Moran Friedman-Gohas, Shirel Weiss, Amir Sternfeld, Astrid Ilguisonis, Danielle Badash, Noa Geffen, Ron Ofri, Yaniv BarKana, Nitza Goldenberg-Cohen

Research output: Contribution to journalArticlepeer-review

Abstract

Decreased blood flow to the optic nerve (ON) and neuroinflammation are suggested to play an important role in the pathophysiology of glaucoma. This study investigated the potential neuroprotective effect of azithromycin, an anti-inflammatory macrolide, and sildenafil, a selective phosphodiesterase-5 inhibitor, on retinal ganglion cell survival in a glaucoma model, which was induced by microbead injection into the right anterior chamber of 50 wild-type (WT) and 30 transgenic toll-like receptor 4 knockout (TLR4KO) mice. Treatment groups included intraperitoneal azithromycin 0.1 mL (1 mg/0.1 mL), intravitreal sildenafil 3 µL, or intraperitoneal sildenafil 0.1 mL (0.24 μg/3 µL). Left eyes served as controls. Microbead injection increased intraocular pressure (IOP), which peaked on day 7 in all groups and on day 14 in azithromycin-treated mice. Furthermore, the retinas and ON of microbead-injected eyes showed a trend of increased expression of inflammatory- and apoptosis-related genes, mainly in WT and to a lesser extent in TLR4KO mice. Azithromycin reduced the BAX/BCL2 ratio, TGFβ, and TNFα levels in the ON and CD45 expression in WT retina. Sildenafil activated TNFα-mediated pathways. Both azithromycin and sildenafil exerted a neuroprotective effect in WT and TLR4KO mice with microbead-induced glaucoma, albeit via different pathways, without affecting IOP. The relatively low apoptotic effect observed in microbead-injected TLR4KO mice suggests a role of inflammation in glaucomatous damage.

Original languageAmerican English
Article number486
JournalPharmaceuticals
Volume16
Issue number4
DOIs
StatePublished - Apr 2023

Keywords

  • azithromycin
  • glaucoma
  • microbeads
  • neuroprotection
  • sildenafil

All Science Journal Classification (ASJC) codes

  • Drug Discovery
  • Molecular Medicine
  • Pharmaceutical Science

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