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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
[217, 218]
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
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
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
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
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)
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
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)
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
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)
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
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
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
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
  1. AP-1 = activator protein 1; Bax = bcl-2 associated x; Bcl-2 = b-cell lymphoma-2; C1 = complement component 1; C1Q = complement component 1Q; COX-2 = cyclooxygenase-2; ET-1 = endothelin-1; IOP = intraocular pressure; IL = interleukin; iNOS = inducible nitric oxide synthase; JNK = c-Jun N-terminal kinase; NF-κB = nuclear factor kappa B; NLRP = NOD-, LRR-family pyrin domain; NMDA = N-methyl-d-aspartate; MCP = monocyte chemotactic protein; MIP = macrophage inflammatory protein; RGC = retinal ganglion cell; TNF = tumor necrosis factor; TLR = Toll-like receptor; OHT = ocular hypertension; ONH = optic nerve head