Description
Purpose: Celastrol, a quinone methide triterpenoid isolated from Tripterygium wilfordii, possesses antioxidant, anti inflammatory and anti apoptotic properties, making it a promising neuroprotective candidate for retinal neurodegenerative diseases such as glaucoma. However, effective therapeutic rescue and preservation of retinal ganglion cells (RGCs) remain an unmet clinical need. The partial optic nerve transection (pONT) model is a well established model of primary and secondary RGC degeneration. This study evaluated the neuroprotective efficacy of a novel nanoformulated Celastrol eye drop in preserving RGCs following pONT injury.
Methods: Celastrol nanoparticles (Cel NPs) were prepared using a thin film rehydration method and characterised by high performance liquid chromatography, dynamic light scattering, and X ray diffraction. In vitro, R28 cells exposed to cobalt chloride were treated with different concentrations of Cel NPs to assess cytoprotective effects. For in vivo evaluation, Dark Agouti rats subjected to pONT received daily topical treatment for 3 weeks with Cel NP, vehicle, Cel only solution, or nerve growth factor (NGF), alongside untreated pONT and healthy control groups. At the study endpoint, retinal apoptosis was assessed using Detection of Apoptosing Retinal Cells (DARC) imaging. Retinal wholemounts were immunostained for RBPMS to quantify RGC survival and IBA 1 to assess microglial reactivity. Superior and inferior retinal quadrants were analysed separately to distinguish effects on primary and secondary degeneration.
Results: Cel NPs showed an encapsulation efficiency greater than 95% and a particle size below 20 nm. In vitro, Cel NPs at an optimal concentration significantly improved cell viability compared with untreated injured cells. In vivo, treatment preserved RGC survival after pONT, with a more pronounced protective effect in the inferior retina, where RGC density was comparable to that of healthy controls. This regional pattern suggests stronger protection against secondary degeneration. Cel NP treatment also reduced hyper ramified and activated microglia in the inferior retina, indicating partial attenuation of injury associated neuroinflammatory responses.
Conclusions: Topical Cel NP demonstrated neuroprotective potential in the pONT model by reducing RGC loss and modulating microglial activation, with particularly strong effects in retinal regions associated with secondary degeneration.
Lay Abstract
Glaucoma is a major cause of irreversible blindness because it damages retinal ganglion cells, which carry visual signals from the eye to the brain. Since these cells cannot be replaced, treatments that protect them are urgently needed.
In this study, we tested Celastrol, a natural compound with antioxidant and anti inflammatory effects, as a possible treatment for retinal nerve damage. To improve delivery to the eye, we developed a nanoparticle eye drop formulation with particles smaller than 20 nm.
The formulation improved survival of stressed retinal cells in the laboratory. In a rat model of optic nerve injury that mimics glaucoma, Celastrol nanoparticle eye drops preserved retinal ganglion cells better than no treatment. The protective effect was strongest in the retinal region linked to secondary degeneration, and treatment also reduced harmful activation of retinal immune cells.
These findings suggest that Celastrol nanoparticle eye drops may offer a promising non invasive treatment for glaucoma and related eye diseases.
| Lay Title | A New Eye Drop to Protect Vision in Glaucoma |
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| Role | PhD Student |