Abstract
Purpose: Intraocular pressure (IOP) is currently the only modifiable risk factor for glaucoma, yet glaucoma can continue to progress despite controlled IOP. Thus, development of glaucoma neurotherapeutics remains an unmet need. Scutellarin is a flavonoid that can exert neuroprotective effects in the eye and brain. Here, we investigated the neurobehavioral effects of scutellarin treatment in a chronic IOP elevation model.Methods: Ten adult C57BL/6J mice were unilaterally injected with an optically clear hydrogel into the anterior chamber to obstruct aqueous outflow and induce chronic IOP elevation. Eight other mice received unilateral intracameral injection of phosphate-buffered saline only. Another eight mice with hydrogel-induced unilateral chronic IOP elevation also received daily oral gavage of 300 mg/kg scutellarin. Tonometry, optical coherence tomography, and optokinetics were performed longitudinally for 4 weeks to monitor the IOP, retinal nerve fiber layer thickness, total retinal thickness, visual acuity, and contrast sensitivity of both eyes in all three groups.Results: Intracameral hydrogel injection resulted in unilateral chronic IOP elevation with no significant inter-eye IOP difference between scutellarin treatment and untreated groups. Upon scutellarin treatment, the hydrogel-injected eyes showed less retinal thinning and reduced visual behavioral deficits when compared to the untreated, hydrogel-injected eyes. No significant difference in retinal thickness or optokinetic measures was found in the contralateral, non-treated eyes over time or between all groups.Conclusion: Using the non-invasive measuring platform, oral scutellarin treatment appeared to preserve retinal structure and visual function upon chronic IOP elevation in mice. Scutellarin may be a novel neurotherapeutic agent for glaucoma treatment.
Highlights
Glaucoma is a chronic neurodegenerative disease involving progressive loss of retinal ganglion cells (RGC) and injuries to their dendrites and axons [1]
A non-invasive in vivo measurement system was developed for longitudinal assessments of intraocular pressure (IOP) via tonometry, retinal thickness via optical coherence tomography, and visual function via optokinetic behavioral testing immediately before, and at 3 days (IOP only), and 1, 2, 3, and 4 weeks after intracameral hydrogel or phosphate-buffered saline (PBS) injection (Table 1)
When comparing IOP over time (Figure 1D), significant group differences were observed between the PBS group (Group 2) and the two hydrogel groups (Groups 1 and 3) after intracameral injection
Summary
Glaucoma is a chronic neurodegenerative disease involving progressive loss of retinal ganglion cells (RGC) and injuries to their dendrites and axons [1]. Several in vitro and in vivo experiments have attempted to demonstrate the potentials of neuroprotective medications for glaucoma These include the use of alpha 2 adrenergic agonists (e.g., brimonidine) [4], prostaglandin-related compounds (e.g., tafluprost) [5], N-methyl-D-aspartate receptor antagonists (e.g., memantine) [6], calcium channel blockers (e.g., nilvadipine) [7], choline precursor (e.g., citicoline) [8], brain-derived neurotrophic factors [9], and plant extracts [e.g., ginkgo biloba [10], xanthophylls, and flavonoids [11]]. For acute IOP elevation and retinal hypoxia models, scutellarin inhibited the inflammatory reactions by mediating the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome-signaling pathway in vivo and in vitro [21] It promoted RGC survival while down-regulating abnormal retinal microglia activation [21]. Well-controlled experiments on the neuroprotective effects of scutellarin on chronic glaucoma remain lacking
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