Table 1 Recent therapeutic options on anti-inflammatory and neuroprotective effects in experimental models of glaucoma and other ocular disease-associated RGC loss
From: Nanoparticles for the treatment of glaucoma-associated neuroinflammation
Therapeutic agent | Experimental model | Route of delivery | Anti-inflammatory and neuroprotective effects | Refs. |
|---|---|---|---|---|
Magnesium acetyltaurate (MgAT) | Retinal ischemia injury; retinal excitotoxicity injury in rat | Intravitreal injection | • Suppressed ET-1- and NMDA-induced retinal and optic nerve damage through induction of iNOS, suppression of NF-κB p65, p53, AP-1 (c-Jun/c-Fos) signaling pathways, downregulation of TNF-α, IL-1β, IL-6, and caspase-3 • Preserved RGC survival by ~ tenfold in NMDA-induced group • Improved visual function after 7 or 14 days of treatment | |
Dietary supplementation (combination of forskolin, homotaurine, spearmint, and B vitamins) | IOP elevation in mice | Oral | • Maintained IOP at baseline level 2 weeks before and after supplementation • Suppressed elevated IOP-induced NF-κB signaling pathway and reduced caspase-3 activity • Preserved retinal function and 20% RGC survival more than the untreated group | [219] |
Laquinimod (LQ) | Retinal ischemia and reperfusion injury in mice | Topical | • Reduced numbers of activated microglia • Suppressed retinal TNF-α, IL-1β, IL-6, and iNOS levels • Inhibited caspase 8 and NLRP3 in retinae and microglia • Promoted RGC survival ~ 1.9-fold and preserved retinal function | [220] |
ONL1204 (small peptide Fas antagonist) | IOP elevation in mice | Intravitreal injection | • Abrogated microglial activation by ~ 1.9-fold • Downregulated cytokines and chemokines, macrophage inflammatory protein (MIP), MIP-1α, MIP-1β, MIP-2, monocyte chemoattractant protein-1 (MCP1), interferon gamma-induced protein 10 (IP10), TNF-α, IL-1β, IL-6, and IL-18), caspase-8, components of the complement cascade (C3 and C1Q), TLR4, and NLRP3 • Prevented axon degeneration (P < 0.0001) and preserved RGC survival (P < 0.001) • No significant different in IOP | [221] |
Apolipoprotein E (ApoE)-mimic peptide COG1410 | Optic nerve crush injury in mice | Intravenous injection | • Reduced JNK phosphorylation, TNF-α, IL-1β, IL-6, iNOS, and Bax/Bcl-2 ratio • Promoted RGC survival by ~ 61% and reduced optic nerve damage (P < 0.05) • Preserved visual function | [222] |
Caffeic acid phenethyl ester | Optic nerve crush injury in rat | Intraperitoneal injection | • Downregulated retinal glia-mediated NF-κB activation, IL-8, IL-6, iNOS, COX-2, and TNF-α • Attenuated gliosis (P < 0.01) • Enhanced RGC survival (P < 0.001) | [223] |
Green tea extract (Theaphenon E) | Retinal ischemia and reperfusion injury in rat | Intragastric administration | • Downregulated TLR4, TNF-α, and IL-1β levels • Reduced expression of cleaved Caspase-3 and Caspase-8 • Downregulated expression Superoxide dismutase 2 (SOD-2), Janus kinase (Jak) and p38 • Enhanced RGC survival (P < 0.001) in ischemic retina | [224] |
Kaempferol | Retinal ischemia and reperfusion injury in mice | Intragastric administration | • Downregulated expression levels of TLR4, TNF-α, IL-1β and IL-6 • Inhibited activation of NF-kB and JNK signaling pathways • Reduced active caspase-3 and caspase-8 • Prevented NLRP1/NLRP3 inflammasome activity • Prevented IOP-induced RGC death (P < 0.01) | [225] |
Minocycline | Retinal vein occlusion in rat; retinal ischemia–reperfusion injury in mice | Intravenous injection | • Reduced activation of microglia • Reduced RGC loss (~ 45%, P < 0.05) • Improved visual function | [226] |
Omega-3 polyunsaturated fatty acids | Anterior ischemic optic nerve injury in rat | Oral gavage | • Downregulated TNF-α, IL-1β, and iNOS levels • Reduced macrophage polarization • Survival of RGC in central and midperipheral retinas was ~ 2.3—(P = 0.03) and 2.0-fold (P = 0.03) higher • Reduced postinfarct apoptosis of RGCs by ~ 2.9-fold (P = 0.007) | [227] |
Synthetic sterol (HE3286) | IOP elevation in rat | Oral gavage | • Maintained IOP at baseline level (P = 0.997) after oral delivery • Increased brain-derived neurotrophic factor (BDNF) expression and reduced TNF-α expression in the ONH • Reduced retinal IL-6, IL-1β, and p75 expression levels • Reduced microglia activation and reduced NF-kB localization • Increased NF-kB localization to neuronal nuclei in the superior colliculus and retina | [228] |
4-(Phenylsulfanyl)butan-2-one | Optic nerve crush in rat | Subcutaneous injection | • Inhibited iNOS/COX-2 pathway in microglia • Increased RGC survival by ~ 36% in the central retina and ~ 35% in the mid-peripheral retina • Reduced RGC apoptosis by ~ 2.2-fold • Preserved visual function • No data on IOP comparison | [229] |
Caffeine | Ocular hypertension in rat | Oral | • Partially reduced IOP level ~ 1.3-fold (P < 0.001) • Inhibited OHT-induced microglial activation • Reduced retinal TNF-α, IL-1β, and iNOS expression levels • Preserved RGC loss by ~ 1.8-fold (P < 0.05) but not RGC retrograde transport | [65] |
Granulocyte colony-stimulating factor (G-CSF) | Optic nerve crush injury in rat | Subcutaneous injection | • Suppressed microglia activity • Downregulated TNF-α, IL-1β and iNOS expressions • Protected RGC from secondary degeneration injury by ~ 38% (P < 0.01) • No data on IOP comparison | [230] |