Protective effects of triptolide on retinal ganglion cells in a rat model of chronic glaucoma

Glaucoma is the leading cause of irreversible blindness worldwide. Elevated intraocular pressure (IOP) is one of the major risk factors for glaucoma onset and progression, and available pharmaceutical interventions are exclusively targeted at IOP lowering. However, degeneration of retinal ganglion cells (RGCs) may continue to progress despite extensive lowering of IOP. A complementary strategy to IOP reduction is the use of neuroprotective agents that interrupt the process of cell death by mechanisms independent of IOP. Here, we describe an ion complexation approach for formulating microcrystals containing ~50% loading of a protein kinase inhibitor, sunitinib, to enhance survival of RGCs with subconjunctival injection. A single subconjunctival injection of sunitinib-pamoate complex (SPC) microcrystals provided 20 weeks of sustained retina drug levels, leading to neuroprotection in a rat model of optic nerve injury. Furthermore, subconjunctival injection of SPC microcrystals also led to therapeutic effects in a rat model of corneal neovascularization. Importantly, therapeutically relevant retina drug concentrations were achieved with subconjunctival injection of SPC microcrystals in pigs. For a chronic disease such as glaucoma, a formulation that provides sustained therapeutic effects to complement IOP lowering therapies could provide improved disease management and promote patient quality of life.

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Protective effects of ciliary neurotrophic factor on the retinal ganglion cells by injure of hydrogen peroxide

International Journal of Ophthalmology ◽

10.18240/ijo.2018.06.05 ◽

2018 ◽

Keyword(s):

Hydrogen Peroxide ◽

Retinal Ganglion Cells ◽

Neurotrophic Factor ◽

Ganglion Cells ◽

Ciliary Neurotrophic Factor ◽

Protective Effects ◽

Retinal Ganglion

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Brimonidine enhances inhibitory postsynaptic activity of OFF- and ON-type retinal ganglion cells in a Wistar rat chronic glaucoma model

Experimental Eye Research ◽

10.1016/j.exer.2019.107833 ◽

2019 ◽

Vol 189 ◽

pp. 107833 ◽

Cited By ~ 4

Author(s):

Xujiao Zhou ◽

Ting Zhang ◽

Jihong Wu

Keyword(s):

Retinal Ganglion Cells ◽

Ganglion Cells ◽

Wistar Rat ◽

Retinal Ganglion ◽

Chronic Glaucoma ◽

Postsynaptic Activity

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Valproate promotes survival of retinal ganglion cells in a rat model of optic nerve crush

Neuroscience ◽

10.1016/j.neuroscience.2012.07.056 ◽

2012 ◽

Vol 224 ◽

pp. 282-293 ◽

Cited By ~ 31

Author(s):

Z.Z. Zhang ◽

Y.Y. Gong ◽

Y.H. Shi ◽

W. Zhang ◽

X.H. Qin ◽

...

Keyword(s):

Optic Nerve ◽

Retinal Ganglion Cells ◽

Rat Model ◽

Ganglion Cells ◽

Optic Nerve Crush ◽

Retinal Ganglion ◽

Nerve Crush

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Rutin prevents retinal ganglion cell death and exerts protective effects by regulating transforming growth factor-β2/Smad2/3Akt/PTEN signaling in experimental rat glaucoma

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v18i5.11 ◽

2021 ◽

Vol 18 (5) ◽

pp. 985-993

Author(s):

Ying Li ◽

Leilei Qin ◽

Liang Ying ◽

Hanguang Dong ◽

Dabo Wang

Keyword(s):

Protective Effect ◽

Rat Model ◽

Transforming Growth Factor ◽

Ganglion Cells ◽

Protective Effects ◽

Retinal Ganglion ◽

Sprague Dawley ◽

Apoptotic Pathway ◽

Ganglion Cell Death

Purpose: To investigate the protective effect of rutin against glaucoma in a rat model, and the mechanisms involved. Methods: Sprague-Dawley rats were injected hypertonic saline in the limbal vein for elevation of intraocular pressure (IOP). Rats in the treatment group were administered rutin at doses of 12.5, 25 or 50 mg/kg orally and daily for 21 days. Results: Rutin markedly (p < 0.05) reduced IOP and prevented loss of retinal ganglion cells (RGCs). The expression of apoptotic pathway proteins, i.e., Bcl-xL, Bcl-2, Bad and Bax were significantly (p < 0.05) regulated by rutin. Moreover, rutin caused a substantial decrease in TGF-β2 expression, and also down-regulated p-Smad2 and p-Smad3 dose-dependently (p < 0.05). Raised levels of collagen I, fibronectin and elastin were effectively down-regulated. Rutin substantially up-regulated the Akt pathway involved in cell survival, and markedly improved the survival of RGCs subjected to hypoxia in vitro (p < 0.05). Conclusion: These results reveal that rutin exerts protective effect against glaucoma in a rat model via a mechanism involving regulation of the TGF-β2/Smad2/3Akt/PTEN signaling pathways. Thus, rutin has potentials for use in the management of glaucoma.

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