Bi-functional small molecule with both IOP lowering and neuroprtective activity to treat glaucoma.
dc.contributor.author | Stankowska, Dorota | |
dc.contributor.author | Millar, Cameron | |
dc.contributor.author | Chaphalkar, Renuka | |
dc.contributor.author | Li, Linya | |
dc.contributor.author | Ellis, Dorette | |
dc.contributor.author | Yorio, Thomas | |
dc.creator | Acharya, Suchismita | |
dc.date.accessioned | 2019-08-22T20:08:32Z | |
dc.date.available | 2019-08-22T20:08:32Z | |
dc.date.issued | 2018-03-14 | |
dc.date.submitted | 2018-02-14T17:38:38-08:00 | |
dc.description.abstract | Purpose: The multifaceted pathology associated with glaucoma is difficult to treat by monotherapy such as lowering intraocular pressure (IOP). Oxidative stress is involved in IOP elevation and retinal ganglion cell (RGC) death possibly via decreased activity of antioxidant enzymes. Our hypothesis is that, a small hybrid molecule SA-2 and its PLGA encapsulated nanoparticle (NP) drug delivery vehicle (SA-2-NPs) possessing a nitric oxide (NO) donating group and a redox antioxidant moiety will lower IOP as well as possess neuro/cytoprotective potential. Methods: IOP-independent neuroprotection of RGCs: Mice (C57BL6, 12 weeks, n=8) were anesthetized and the optic nerve crush (ONC) was performed on one eye followed by intravitreal injection of 2ml of 2% SA-2 formulated in PBS or vehicle to the crushed eye at day 0 and 3. At day 7, pattern electroretinogram (PERG) was performed, following which retinas were flat mounted. Number of surviving, RBPMS positive RGCs were counted. IOP lowering effect: Nine Brown Norway normotensive rats (n=3 per each group) were used to evaluate the IOP-lowering properties of SA-2-NPs under a masked protocol. Topical eye drops (30 µL/drop) containing: A) Vehicle (PBS), B) Travoprost (0.004%)-positive control or C) SA-2-NPs (100 µg/mL) formulated in PBS were administered in three rats and IOP was measured using the TonoLab rebound tonometer at various time points: 0, 3, 6, 24, 48 and 72 h post-dosing. The entire dosing schedule was repeated 3 times in each rat. Results: Compound SA-2 treatment was significantly (t-test, p 2 vs SA-2 treated group (2100 cells/cm2) and was comparable to the untreated control (2650 cells/cm2). The data are given as the mean ± SEM; n= 3-4. PLGA encapsulated SA-2-NPs (100mg) statistically (t-test, p Conclusion: Taken together, our results are consistent with our hypothesis that this novel class of hybrid compound and its PLGA encapsulated nanoparticles will decrease IOP and protect RGCs from cell death. Further structure optimization of the lead compound, dose optimization, IOP lowering study in ocular hypertensive rodent models are underway. | |
dc.identifier.uri | https://hdl.handle.net/20.500.12503/27895 | |
dc.language.iso | en | |
dc.provenance.legacyDownloads | 0 | |
dc.title | Bi-functional small molecule with both IOP lowering and neuroprtective activity to treat glaucoma. | |
dc.type | poster | |
dc.type.material | text |