Oral Scutellarin Treatment Ameliorates Retinal Thinning and Visual Deficits in Experimental Glaucoma

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.

Reverse translation of artificial intelligence in glaucoma: Connecting basic science with clinical applications

“…Tree shrews may be considered as an alternative glaucoma animal model given the presence of the laminar cribrosa in the eyes of these small animals ( 27 ). The ability to access refined measurements of glaucoma pathology in a longitudinal and non-invasive manner could improve the usability of these models moving forward ( 91 – 93 ).…”

Based on multiple machine learning to identify the ENO2 as diagnosis biomarkers of glaucoma

“…7-O-Methylisomucronulatol was key compound in the compound-target network of Qing Guang An Granule (QGAG) to the treatment of glaucoma [ 36 ]. Scutellarin was discovered as a substance that protects the nerves of the eyes and brain, which is a new neurotherapeutic agent for glaucoma treatment, it has been studied in mice, at present, [ 37 , 38 ]. Acetylsalicylic acid has complex effects on the changes of intraocular pressure, studies have demonstrated that single-use of acetylsalicylic acid cannot significantly reduce intraocular pressure in glaucoma patients, but long-term use will have an impact on intraocular pressure [ 39 , 40 ].…”

Current advances on the therapeutic potential of scutellarin: an updated review

“…Scutellarin also has pharmacological activities such as treatment of glaucoma, liver protection, kidney protection, and hyperuricemia. Zhu et al established a mouse model of glaucoma and found that scutellarin could maintain the retinal structure and visual function of mice when intraocular pressure was elevated, suggesting that scutellarin is a potentially novel neurotherapeutic agent used in the treatment of glaucoma [ 90 ]. Li et al found that scutellarin reduced renal injury and lowered the glomerular filtration rate in hyperuricemic mice (HN), which may be alleviated by a regulatory mechanism of extracellular cellular communication network factor 1 (CCN1) on the activation of NLRP3 inflammatory vesicles [ 91 ].…”