Therapeutic Targeting of Retinal Immune Microenvironment With CSF-1 Receptor Antibody Promotes Visual Function Recovery After Ischemic Optic Neuropathy

Tang, Yizhen; Xiao, Zhang; Pan, Li; Zhuang, Dazhong; Cho, Kin‐Sang; Kyle, Robert H.; Chen, Xiaoxiao; Shu, Lian; Tang, Guangxian; Wu, Jihong; Sun, Xinghuai; Chen, Dong F.

doi:10.3389/fimmu.2020.585918

Cited by 19 publications

(28 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with previous studies, deficits of retinal physiological responses and spatial visual functions commonly occur in retinal I/R injury (5,18,59,60). Our results demonstrated the potent therapeutic capacities of baicalein following I/R insults, as reflected by increased RGC density, retinal physiological functions, visual acuity, and contrast sensitivity.…”

Section: Discussionsupporting

confidence: 92%

“…We have recently shown that excessive microglia activationinduced retinal neuroinflammation presents as a primary pathological factor leading to retinal degeneration in retinal I/R injury (18). Maintaining the homeostasis of the retinal immune microenvironment is an appealing therapeutic option to alleviate neuronal degeneration and to maintain retinal function, such as through targeting colony stimulator factor 1 receptor (CSF1R) or neutralizing infiltrated CD4 + T cells (5,18,50). Consistent with other reports (51)(52)(53)(54)(55), the upregulated expression of Iba-1, Ptgs2, Nox2, Tlr4, and Ym1, which are known to be sensitive markers of microglia activation, was detected in injured retina in our study.…”

Section: Discussionmentioning

confidence: 99%

“…Despite the eyes being regarded as an immune-privileged site, it has been shown that the compromise of the blood retinal barrier under stress allows for the recruitment of peripheral immune cells to the lesion site and triggers adaptive immune responses, ultimately aggravating neuronal death (5,30). We previously reported that retinal infiltration of CD4 + T cells peaked at 2 weeks post-I/R injury (5,18). In the present study, we showed that baicalein significantly suppressed Th17 (CD4 + IL- B).…”

Section: Baicalein Alleviates Retinal I/r Injury-induced Retinal Micr...mentioning

confidence: 99%

See 2 more Smart Citations

Baicalein—A Potent Pro-Homeostatic Regulator of Microglia in Retinal Ischemic Injury

et al. 2022

Self Cite

View full text Add to dashboard Cite

Retinal ischemia is a common cause of many retinal diseases, leading to irreversible vision impairment and blindness. Excessive neuroinflammation, including microglial activation and T-cell responses, has been identified as a critical factor associated with neurodegeneration in retinal ischemia. Baicalein is a natural flavonoid reported to have broad anti-inflammatory and neuroprotective bioactivities. Herein, the effects of baicalein on microglia activation in vitro and in vivo were investigated. We found that baicalein exhibited robust anti-inflammatory effect on cultured human and mouse microglia, as demonstrated by decreased induction of pro-inflammatory cytokines and the phosphorylation of phosphoinositide 3-kinase (PI3K) and nuclear factor kappa B (NFκB). Proteomic analysis further unraveled baicalein’s effect on modulating IL-17 signaling pathways and its upstream regulator IL-1β. Intravitreal administration of baicalein in the mouse model of retinal ischemia/reperfusion (I/R) injury attenuated microglial activation and retinal T-cell infiltration, particularly the T helper 17 cells. Additionally, baicalein was shown to exert neuroprotective effects by significantly reducing the retinal ganglion cell (RGC) loss after I/R injury, leading to an improved retinal function and spatial vision. These results suggest that baicalein, a natural flavonoid, acts as a negative regulator of activated microglia and immune responses both in vitro and in vivo, effectively alleviating neurodegeneration in retinal I/R injury. This finding indicates that baicalein could be a potential therapeutic agent against currently incurable degenerative retinal diseases.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Baicalein Alleviates Retinal I/r Injury-induced Retinal Micr...mentioning

confidence: 99%

See 1 more Smart Citation

Baicalein—A Potent Pro-Homeostatic Regulator of Microglia in Retinal Ischemic Injury

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…Future studies should include larger sample sizes, especially of patients with acute NAION, and patients with other acute optic nerve head pathologies in order to investigate whether blood inflammatory changes are specific of NAION and therefore can be used to develop an accurate diagnostic tool. Because inhibition of specific cytokine-receptor binding in the eye has proven beneficial in an animal model of retina-ischemic reperfusion, 35 drug targeting of selected molecules in animal models of NAION and the study of their neuroprotective effects will contribute to the development of new treatment opportunities.…”

Section: Discussionmentioning

confidence: 99%

Immunoprofiling of Nonarteritic Anterior Ischemic Optic Neuropathy

Mesentier-Louro

Stell

Yan

et al. 2021

Trans. Vis. Sci. Tech.

View full text Add to dashboard Cite

Nonarteritic anterior ischemic optic neuropathy (NAION) is a common acute optic neuropathy in those older than 50 years. There is no blood diagnostic test or efficient treatment for NAION. We investigated the suitability of blood inflammatory proteins as biomarkers and therapeutic targets of NAION. Methods:We conducted an exploratory, cross-sectional case-control study including 18 patients with NAION (n = 5 acute, and n = 13 chronic) and 9 controls. NAION was confirmed by clinical examination and optical coherence tomography. Subjects underwent peripheral blood collection; plasma was isolated within 2 hours and analyzed using a 76-plex array of cytokines, chemokines, and growth factors.Results: In acute NAION, there was increased peripapillary retinal thickness on optical coherence tomography consistent with optic disc edema. Plasma profiling revealed dramatic changes in inflammatory proteins in NAION. Statistical analysis generated a list of 20 top-ranked molecules in NAION, with 15% overlap in acute and chronic NAION. Principal component analysis, hierarchical clustering, and Spearman correlation generally segregated controls, acute and chronic NAION, with some overlap. Longitudinal data from one patient demonstrated an evolving inflammatory pattern from acute to chronic NAION. In acute NAION, Eotaxin-3, MCP-2, TPO, and TRAIL were the top biomarker candidates. In chronic NAION, IL-1α and CXCL10 emerged as the strongest therapeutic targets.Conclusions: Post-NAION inflammation occurs in both acute and chronic NAION. Statistical analysis of plasma profile changes generated a list of 20 potential biomarker and therapeutic targets of NAION. Translational Relevance:We identified blood molecular targets to improve NAION diagnosis and treatment.

show abstract

“…Secondly, the anti-inflammatory effect initiated by these flavonoids after ischemia is revealed by the suppression of proinflammatory cytokine release. Excessive activation of microglia has been emergingly reported as a pathogenesis for the development of neurodegenerative diseases [ 137 ]. In addition, baicalein and baicalin exhibit the capability in regulating microglia homeostasis after ischemic stress [ 109 ].…”

Section: Pathways Targeted By Baicalein Baicalin and Wogonin During Neuroprotective Processesmentioning

confidence: 99%

Baicalein, Baicalin, and Wogonin: Protective Effects against Ischemia‐Induced Neurodegeneration in the Brain and Retina

Pan

Cho

et al. 2021

Oxidative Medicine and Cellular Longevity

Self Cite

View full text Add to dashboard Cite

Ischemia is a common pathological condition present in many neurodegenerative diseases, including ischemic stroke, retinal vascular occlusion, diabetic retinopathy, and glaucoma, threatening the sight and lives of millions of people globally. Ischemia can trigger excessive oxidative stress, inflammation, and vascular dysfunction, leading to the disruption of tissue homeostasis and, ultimately, cell death. Current therapies are very limited and have a narrow time window for effective treatment. Thus, there is an urgent need to develop more effective therapeutic options for ischemia-induced neural injuries. With emerging reports on the pharmacological properties of natural flavonoids, these compounds present potent antioxidative, anti-inflammatory, and antiapoptotic agents for the treatment of ischemic insults. Three major active flavonoids, baicalein, baicalin, and wogonin, have been extracted from Scutellaria baicalensis Georgi (S. baicalensis); all of which are reported to have low cytotoxicity. They have been demonstrated to exert promising pharmacological capabilities in preventing cell and tissue damage. This review focuses on the therapeutic potentials of these flavonoids against ischemia-induced neurotoxicity and damage in the brain and retina. The bioactivity and bioavailability of baicalein, baicalin, and wogonin are also discussed. It is with hope that the therapeutic potential of these flavonoids can be utilized and developed as natural treatments for ischemia-induced injuries of the central nervous system (CNS).

show abstract

Therapeutic Targeting of Retinal Immune Microenvironment With CSF-1 Receptor Antibody Promotes Visual Function Recovery After Ischemic Optic Neuropathy

Cited by 19 publications

References 61 publications

Baicalein—A Potent Pro-Homeostatic Regulator of Microglia in Retinal Ischemic Injury

Baicalein—A Potent Pro-Homeostatic Regulator of Microglia in Retinal Ischemic Injury

Immunoprofiling of Nonarteritic Anterior Ischemic Optic Neuropathy

Baicalein, Baicalin, and Wogonin: Protective Effects against Ischemia‐Induced Neurodegeneration in the Brain and Retina

Contact Info

Product

Resources

About