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Azithromycin and Sildenafil May Have Protective Effects on Retinal Ganglion Cells via Different Pathways: Study in a
Tal Corina Sela1,2, Alon Zahavi2,3,4, Moran Friedman-Gohas2,5
1Clalit Health Services, Tel Aviv 6209804, Israel.
Pharmaceuticals (Basel, Switzerland)
|April 28, 2023
Summary
Azithromycin and sildenafil show neuroprotective effects in a mouse glaucoma model by reducing inflammation and apoptosis. These treatments support retinal ganglion cell survival via distinct pathways without altering intraocular pressure.
Area of Science:
- Ophthalmology
- Neuroscience
- Pharmacology
Background:
- Glaucoma pathophysiology involves optic nerve (ON) hypoperfusion and neuroinflammation.
- Retinal ganglion cell (RGC) survival is critical in glaucoma management.
Purpose of the Study:
- To investigate the neuroprotective potential of azithromycin and sildenafil in a microbead-induced glaucoma mouse model.
- To elucidate the mechanisms underlying their effects on RGC survival and inflammation.
Main Methods:
- Glaucoma was induced using microbead injection in wild-type (WT) and toll-like receptor 4 knockout (TLR4KO) mice.
- Mice received intraperitoneal azithromycin or intraperitoneal/intravitreal sildenafil.
- Gene expression, protein levels (BAX/BCL2, TGFβ, TNFα), and CD45 expression were analyzed.
Main Results:
- Microbead injection increased intraocular pressure (IOP) and inflammatory/apoptotic gene expression, particularly in WT mice.
- Azithromycin decreased BAX/BCL2 ratio, TGFβ, TNFα, and CD45 expression.
- Sildenafil activated TNFα-mediated pathways.
- Both drugs demonstrated neuroprotection without affecting IOP.
Conclusions:
- Azithromycin and sildenafil offer neuroprotection in glaucoma via distinct inflammatory and apoptotic pathways.
- Reduced inflammation in TLR4KO mice correlated with lower apoptotic effects, highlighting inflammation's role in glaucomatous damage.
