Citicoline Modulates Glaucomatous Neurodegeneration Through Intraocular Pressure-Independent Control

Merwe, Yolandi van der; Murphy, Matthew; Sims, Jeffrey R.; Faiq, Muneeb A.; Yang, Xiao Ling; Ho, Leon C.; Yu, Yu; Leung, Christopher Kin Ying; Wollstein, Gadi; Schuman, Joel S.; Chan, Kevin C.

doi:10.1007/s13311-021-01033-6

Cited by 22 publications

(10 citation statements)

References 92 publications

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“…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 ).…”

Section: Discussionmentioning

confidence: 99%

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

Pasquale

Girard

et al. 2023

Front. Ophthalmol.

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Artificial intelligence (AI) has been approved for biomedical research in diverse areas from bedside clinical studies to benchtop basic scientific research. For ophthalmic research, in particular glaucoma, AI applications are rapidly growing for potential clinical translation given the vast data available and the introduction of federated learning. Conversely, AI for basic science remains limited despite its useful power in providing mechanistic insight. In this perspective, we discuss recent progress, opportunities, and challenges in the application of AI in glaucoma for scientific discoveries. Specifically, we focus on the research paradigm of reverse translation, in which clinical data are first used for patient-centered hypothesis generation followed by transitioning into basic science studies for hypothesis validation. We elaborate on several distinctive areas of research opportunities for reverse translation of AI in glaucoma including disease risk and progression prediction, pathology characterization, and sub-phenotype identification. We conclude with current challenges and future opportunities for AI research in basic science for glaucoma such as inter-species diversity, AI model generalizability and explainability, as well as AI applications using advanced ocular imaging and genomic data.

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Section: Discussionmentioning

confidence: 99%

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

Pasquale

Girard

et al. 2023

Front. Ophthalmol.

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“…In the current study, we applied oral scutellarin treatment to our recently developed experimental glaucoma model, and demonstrated the preservation of retinal structure and visual function by scutellarin via non-invasive assessments over time. This crosslinking hydrogel model produces chronic IOP elevation while preserves optical media clarity in the long term (22). The transparency of the bioinert hydrogel allows not only in vivo optical imaging of the retina but also longitudinal evaluation of awake optokinetic responses, both of which are important for understanding glaucomatous neurodegeneration and treatment effects.…”

Section: Discussionmentioning

confidence: 99%

“…To date, pre-clinical testing of glaucoma neurotherapeutics has been limited by existing experimental models that allow chronic elevation of IOP while preserving optical media clarity for non-invasive and longitudinal evaluation of the structure and function of the visual system. Recently, we have developed a novel experimental glaucoma rodent model that satisfies the above requirements via intracameral injection of an optically clear, cross-linked hydrogel ( 22 , 23 ). In the current study, we used this experimental model in combination with non-invasive imaging and behavioral assessments to investigate if scutellarin is neuroprotective against chronic experimental glaucoma.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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.

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“…The efficacy of citicoline in protecting the axons of the visual pathway has been demonstrated in an experimental model of glaucoma. This model involved the acute elevation of the IOP via anterior chamber perfusion with physiological saline in rats [ 27 ]. In this model, after the IOP elevation, different changes in the visual pathway were observed, such as alterations in myelin density and axon integrity and a decrease in anterograde axonal transport.…”

Section: Citicoline and Coq10: Relationship With Retinal Diseasesmentioning

confidence: 99%

The Role of Citicoline and Coenzyme Q10 in Retinal Pathology

García-López

Matamoros

et al. 2023

IJMS

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Ocular neurodegenerative diseases such as glaucoma, diabetic retinopathy, and age-related macular degeneration are common retinal diseases responsible for most of the blindness causes in the working-age and elderly populations in developed countries. Many of the current treatments used in these pathologies fail to stop or slow the progression of the disease. Therefore, other types of treatments with neuroprotective characteristics may be necessary to allow a more satisfactory management of the disease. Citicoline and coenzyme Q10 are molecules that have neuroprotective, antioxidant, and anti-inflammatory properties, and their use could have a beneficial effect in ocular neurodegenerative pathologies. This review provides a compilation, mainly from the last 10 years, of the main studies that have been published on the use of these drugs in these neurodegenerative diseases of the retina, analyzing the usefulness of these drugs in these pathologies.

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Citicoline Modulates Glaucomatous Neurodegeneration Through Intraocular Pressure-Independent Control

Cited by 22 publications

References 92 publications

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

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

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

The Role of Citicoline and Coenzyme Q10 in Retinal Pathology

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