Modulation of the Immune System for the Treatment of Glaucoma

Bell, Katharina; Hohenstein-Blaul, Nadine von Thun und; Teister, Julia; Grus, Franz H.

doi:10.2174/1570159x15666170720094529

Cited by 36 publications

(23 citation statements)

References 136 publications

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“…The blockade of the microglial adenosine A 2A receptor has been shown to protect RGCs from elevated IOP in murine glaucoma models by controlling the microglial activation and inhibiting reactive oxygen species ( 214 ). Minocycline has also been shown to inhibit microglial activation and upregulate pro-survival genes in experimental glaucoma ( 215 , 216 ). Although minocycline has proven oral safety and has been found to cross the blood–brain barrier, long-term randomized control trials with the necessary high doses of minocycline are needed ( 217 ).…”

Section: Therapeutic Approachesmentioning

confidence: 99%

Glial Cells in Glaucoma: Friends, Foes, and Potential Therapeutic Targets

et al. 2021

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Glaucoma is the second leading cause of blindness worldwide, affecting ~80 million people by 2020 (1, 2). The condition is characterized by a progressive loss of retinal ganglion cells (RGCs) and their axons accompanied by visual field loss. The underlying pathophysiology of glaucoma remains elusive. Glaucoma is recognized as a multifactorial disease, and lowering intraocular pressure (IOP) is the only treatment that has been shown to slow the progression of the condition. However, a significant number of glaucoma patients continue to go blind despite intraocular pressure-lowering treatment (2). Thus, the need for alternative treatment strategies is indisputable. Accumulating evidence suggests that glial cells play a significant role in supporting RGC function and that glial dysfunction may contribute to optic nerve disease. Here, we review recent advances in understanding the role of glial cells in the pathophysiology of glaucoma. A particular focus is on the dynamic and essential interactions between glial cells and RGCs and potential therapeutic approaches to glaucoma by targeting glial cells.

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Section: Therapeutic Approachesmentioning

confidence: 99%

Glial Cells in Glaucoma: Friends, Foes, and Potential Therapeutic Targets

et al. 2021

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“…How retinal microglia transition from a homeostatic physiological state to ones that promote disease progression is however not well understood. Elucidation of molecular mechanisms governing these transitions is likely central to designing strategies for microglial modulation in retinal disease (Arroba and Valverde, 2017; Bell et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Absence of TGFβ signaling in retinal microglia induces retinal degeneration and exacerbates choroidal neovascularization

Silverman

Zhao

et al. 2019

eLife

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Constitutive TGFβ signaling is important in maintaining retinal neurons and blood vessels and is a factor contributing to the risk for age-related macular degeneration (AMD), a retinal disease involving neurodegeneration and microglial activation. How TGFβ signaling to microglia influences pathological retinal neuroinflammation is unclear. We discovered that ablation of the TGFβ receptor, TGFBR2, in retinal microglia of adult mice induced abnormal microglial numbers, distribution, morphology, and activation status, and promoted a pathological microglial gene expression profile. TGFBR2-deficient retinal microglia induced secondary gliotic changes in Müller cells, neuronal apoptosis, and decreased light-evoked retinal function reflecting abnormal synaptic transmission. While retinal vasculature was unaffected, TGFBR2-deficient microglia demonstrated exaggerated responses to laser-induced injury that was associated with increased choroidal neovascularization, a hallmark of advanced exudative AMD. These findings demonstrate that deficiencies in TGFβ-mediated microglial regulation can drive neuroinflammatory contributions to AMD-related neurodegeneration and neovascularization, highlighting TGFβ signaling as a potential therapeutic target.

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“…First, the most important risk factor for glaucoma is elevated intraocular pressure, but there are other important factors including inflammation, which may link glaucoma with cancer. Inflammation plays a role in the pathogenesis of glaucoma, in which low grade chronic inflammation occurs in www.nature.com/scientificreports www.nature.com/scientificreports/ response to elevated intraocular pressure and vascular dysfunction 24,25 . In healthy eyes, the blood-ocular barrier prevents many molecular substances from crossing from the blood into the eye and vice versa, but in glaucomatous eyes, this barrier around the optic nerve head has been shown to leak 26 .…”

Section: Discussionmentioning

confidence: 99%

Risk of cancer in patients with glaucoma: A nationwide population-based cohort study

Jung

Han

et al. 2020

Sci Rep

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to compare the risk of cancer development between patients with glaucoma and those without, we conducted a nationwide population-based cohort study using the Korean national Health insurance Database. Individuals with diagnosis of glaucoma between 2007 and 2016 were identified, and controls were 1:1 matched based on age and sex. We calculated the incidence rates(IR) and hazard ratios(HR) before and after adjusting for age, gender, diabetes, smoking history, and body mass index. A total of 107,536 individuals with glaucoma and the same number of individuals without glaucoma were included. The IR of overall cancer were 12.23 and 11.62 per 1,000 individuals in the glaucoma and control groups, respectively. The HR of overall cancer was significantly higher in the glaucoma group before(HR: 1.053) and after adjusting for confounding factors(adjusted HR: 1.049) compared to that in the control group. The risk of overall cancer and specific cancers varied depending on gender and age groups, and the association was stronger in women and those under 65 years of age. Our study revealed that individuals with glaucoma showed higher risk of overall cancer and higher risk of specific cancers than those without glaucoma.

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Modulation of the Immune System for the Treatment of Glaucoma

Cited by 36 publications

References 136 publications

Glial Cells in Glaucoma: Friends, Foes, and Potential Therapeutic Targets

Glial Cells in Glaucoma: Friends, Foes, and Potential Therapeutic Targets

Absence of TGFβ signaling in retinal microglia induces retinal degeneration and exacerbates choroidal neovascularization

Risk of cancer in patients with glaucoma: A nationwide population-based cohort study

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