Cytokine Profiles and the Effect of Intravitreal Aflibercept Treatment on Experimental Choroidal Neovascularization

Wang, Chen; Zhang, Rongrong; Zhang, Qi; Jin, Huixiang; Wei, Chenghua; Wu, Changfan; Mei, Lixin; Liu, Yinping; Zhang, Pengfei

doi:10.1159/000513588

Cited by 4 publications

(4 citation statements)

References 35 publications

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“…MIP-1a was signi cantly correlated with the CNV lesion area, suggesting that the migration of MIP-1a-mediated macrophages could induce an in ammatory response and affect CNV formation. [22] Our novel results showed elevated aqueous humor concentrations of MIP-1α and MIP-1β in eyes with neovascular AMD. We believe that these ndings are attributed to a disrupted RPE cell regulation because of degeneration and suggest that in ammatory factors may in uence the pathogenesis of AMD.…”

Section: Discussionmentioning

confidence: 58%

Aqueous Humor Cytokine Levels Through Microarray Analysis and a Sub-Analysis Based on Optical Coherence Tomography in Wet Age-Related Macular Degeneration Patients

Joo

Kim²,

Shin

et al. 2021

Preprint

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Backgorund To identify disease-specific cytokine and growth factor profile differences in the aqueous humor between wet age-related macular degeneration (AMD) patients and age-matched controls and to correlate their levels with the optical coherence tomography (OCT) findings.MethodsAqueous humors were obtained from 13 wet AMD eyes and 10 control eyes. Twenty cytokines and growth factors were measured using a RayBio antibody microarray technology in wet AMD and control eyes. Results The samples obtained from wet AMD patients exhibited a significantly increased expression of MCP-1, MIP-1α, MIP-1β, and vascular endothelial growth factor (VEGF). Subretinal fluid (SRF) patients showed significantly lower levels of proinflammatory cytokines, such as IL-1α and GM-CSF, than those without SRF. Pigment epithelial detachments (PED) patients showed lower levels of inflammatory cytokines, such as GM-CSF, IFN-γ, and TNF-α, than those without PED. Subretinal tissue (SRT) patients showed a higher level of IFN-γ than those without SRT. Compared with the controls, type 1 choroidal neovascularization (CNV) patients showed increased levels of MCP-1, MIP-1α, and MIP-1β, but not VEGF (p = 0.083). However, type 2 CNV patients showed increased levels of MCP-1 and VEGF (p = 0.040 and p = 0.040). Conclusion Inflammatory cytokines varied according to the type of AMD- and OCT-based parameters. Our observation of low levels of VEGF in patients with type 1 CNV implies that the inhibition of VEGF alone appears to be insufficient treatment for these patients and that cytokines such as MCP-1, MIP-1α, and MIP-1β should be modulated. And the presence of SRF in CNV may be associated with a positive prognosis because we found relatively low levels of proinflammatory cytokines. Thus, treatment decisions for patients with wet AMD should be based on OCT-based biomarkers and angiographic classification schemes, and in patients with wet AMD, which is not treated well with anti-VEGF alone, it is necessary to analyze inflammatory cytokines.

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Section: Discussionmentioning

confidence: 58%

Aqueous Humor Cytokine Levels Through Microarray Analysis and a Sub-Analysis Based on Optical Coherence Tomography in Wet Age-Related Macular Degeneration Patients

Joo

Kim²,

Shin

et al. 2021

Preprint

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“…In addition, it was confirmed that MIP-1a was significantly increased in a study targeting the laser-induced CNV mouse model. MIP-1a was significantly correlated with the CNV lesion area, suggesting that the migration of MIP-1a-mediated macrophages could induce an inflammatory response and affect CNV formatio n [26]. Our novel results showed elevated aqueous humor concentrations of MIP-1α and MIP-1β in eyes with wet AMD.…”

Section: Fig 2 Correlation Between the Volume Of Subretinal Fluid (Sr...mentioning

confidence: 56%

Aqueous humor cytokine levels through microarray analysis and a sub-analysis based on optical coherence tomography in wet age-related macular degeneration patients

Joo

Kim²,

Shin

et al. 2021

BMC Ophthalmol

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Background To identify disease-specific cytokine and growth factor profile differences in the aqueous humor between wet age-related macular degeneration (AMD) patients and age-matched controls and to correlate their levels with the optical coherence tomography (OCT) findings. Methods Aqueous humors were obtained from 13 wet AMD eyes and 10 control eyes. Twenty cytokines and growth factors were measured using a RayBio antibody microarray technology in wet AMD and control eyes. Results The samples obtained from wet AMD patients exhibited a significantly increased expression of MCP-1, MIP-1α, MIP-1β, and vascular endothelial growth factor (VEGF). Subretinal fluid (SRF) patients showed significantly lower levels of proinflammatory cytokines, such as IL-1α and GM-CSF, than those without SRF. Pigment epithelial detachments (PED) patients showed lower levels of inflammatory cytokines, such as GM-CSF, IFN-γ, and TNF-α, than those without PED. Subretinal tissue (SRT) patients showed a higher level of IFN-γ than those without SRT. Compared with the controls, type 1 macular neovascularization (MNV) patients showed increased levels of MCP-1, MIP-1α, and MIP-1β, but not VEGF (p = 0.083). However, type 2 MNV patients showed increased levels of MCP-1 and VEGF (p = 0.040 and p = 0.040). Conclusion Inflammatory cytokines varied according to the type of AMD- and OCT-based parameters. Our observation of low levels of VEGF in patients with type 1 MNV implies that the inhibition of VEGF alone appears to be insufficient treatment for these patients and that cytokines such as MCP-1, MIP-1α, and MIP-1β should be modulated. And the presence of SRF in MNV may be associated with a positive prognosis because we found relatively low levels of proinflammatory cytokines.

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“…These marker genes represent different M2 macrophage subpopulations, suggesting that different macrophage subtypes have distinct roles at different time-points during the pathological process of CNV. Specifically, M2a macrophages may be associated with neovascularisation, whereas M2b and M2c macrophages may be involved in fibrous scarring ( 195 ).…”

Section: Intraocular Neovascularisation-related Diseasesmentioning

confidence: 99%

Role of microglia/macrophage polarisation in intraocular diseases (Review)

Li,

Zheng

2024

Int J Mol Med

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Macrophages form a crucial component of the innate immune system, and their activation is indispensable for various aspects of immune and inflammatory processes, tissue repair, and maintenance of the balance of the body's state. Macrophages are found in all ocular tissues, spanning from the front surface, including the cornea, to the posterior pole, represented by the choroid/sclera. The neural retina is also populated by specialised resident macrophages called microglia. The plasticity of microglia/macrophages allows them to adopt different activation states in response to changes in the tissue microenvironment. When exposed to various factors, microglia/macrophages polarise into distinct phenotypes, each exhibiting unique characteristics and roles. Furthermore, extensive research has indicated a close association between microglia/macrophage polarisation and the development and reversal of various intraocular diseases. The present article provides a review of the recent findings on the association between microglia/macrophage polarisation and ocular pathological processes (including autoimmune uveitis, optic neuritis, sympathetic ophthalmia, retinitis pigmentosa, glaucoma, proliferative vitreoretinopathy, subretinal fibrosis, uveal melanoma, ischaemic optic neuropathy, retinopathy of prematurity and choroidal neovascularization). The paradoxical role of microglia/macrophage polarisation in retinopathy of prematurity is also discussed. Several studies have shown that microglia/macrophages are involved in the pathology of ocular diseases. However, it is required to further explore the relevant mechanisms and regulatory processes. The relationship between the functional diversity displayed by microglia/macrophage polarisation and intraocular diseases may provide a new direction for the treatment of intraocular diseases.

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Cytokine Profiles and the Effect of Intravitreal Aflibercept Treatment on Experimental Choroidal Neovascularization

Cited by 4 publications

References 35 publications

Aqueous Humor Cytokine Levels Through Microarray Analysis and a Sub-Analysis Based on Optical Coherence Tomography in Wet Age-Related Macular Degeneration Patients

Aqueous Humor Cytokine Levels Through Microarray Analysis and a Sub-Analysis Based on Optical Coherence Tomography in Wet Age-Related Macular Degeneration Patients

Aqueous humor cytokine levels through microarray analysis and a sub-analysis based on optical coherence tomography in wet age-related macular degeneration patients

Role of microglia/macrophage polarisation in intraocular diseases (Review)

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