Multiple cytokine analyses of aqueous humor from the patients with retinitis pigmentosa

Yin, Houfa; Tang, Qiaomei; Wang, Wei; Luo, Chenqi; Chen, Xinyi; Zhang, Xiaobo; Lai, Kairan; Xu, Junjie; Chen, Xiangjun; Yao, Ke

doi:10.1016/j.cyto.2019.154943

Cited by 30 publications

(21 citation statements)

References 51 publications

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“…The inflammatory cells contribute to retinal degeneration through their cytotoxic effects on photoreceptors ( 65 ). Increased levels of pro-inflammatory cytokines and chemokines, in addition to anti-retinal AAbs and immune cells, were detected in sera, aqueous humor, and vitreous of the patients with RP ( 18 , 31 , 37 , 66 , 67 ) and in the rodent disease models ( 68 , 69 ). Usually, there is a significant upregulation of the inflammatory markers [interleukin (IL)-1β, IL-6, tumor necrosis factor α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and ionized calcium binding adaptor molecule 1 (IBA1)] by intraocular cells to start the inflammatory processes ( 70 , 71 ).…”

Section: Pathways Contributing To the Death Of Photoreceptorsmentioning

confidence: 99%

Importance of Autoimmune Responses in Progression of Retinal Degeneration Initiated by Gene Mutations

Adamus

2021

Front. Med.

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Inherited retinal diseases (IRDs) are clinically and genetically heterogeneous rare disorders associated with retinal dysfunction and death of retinal photoreceptor cells, leading to blindness. Among the most frequent and severe forms of those retinopathies is retinitis pigmentosa (RP) that affects 1:4,000 individuals worldwide. The genes that have been implicated in RP are associated with the proteins present in photoreceptor cells or retinal pigment epithelium (RPE). Asymmetric presentation or sudden progression in retinal disease suggests that a gene mutation alone might not be responsible for retinal degeneration. Immune responses could directly target the retina or be site effect of immunity as a bystander deterioration. Autoantibodies against retinal autoantigens have been found in RP, which led to a hypothesis that autoimmunity could be responsible for the progression of photoreceptor cell death initiated by a genetic mutation. The other contributory factor to retinal degeneration is inflammation that activates the innate immune mechanisms, such as complement. If autoimmune responses contribute to the progression of retinopathy, this could have an implication on treatment, such as gene replacement therapy. In this review, we provide a perspective on the current role of autoimmunity/immunity in RP pathophysiology.

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Section: Pathways Contributing To the Death Of Photoreceptorsmentioning

confidence: 99%

Importance of Autoimmune Responses in Progression of Retinal Degeneration Initiated by Gene Mutations

Adamus

2021

Front. Med.

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“…Similarly, if the detection rate was ≧ 80% in either of the two groups, the concentrations in the groups were compared by multiplex ELISA, as described in a previous report. 17 …”

Section: Methodsmentioning

confidence: 99%

“…Similarly, if the detection rate was ≧ 80% in either of the two groups, the concentrations in the groups were compared as described in a previous report. 17 Correlations between chemokines and visual parameters were determined by Spearman's rank test. P values < 0.05 were considered significant.…”

Section: Methodsmentioning

confidence: 99%

Changes of Serum Inflammatory Molecules and Their Relationships with Visual Function in Retinitis Pigmentosa

Okita

Murakami

Shimokawa

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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Purpose Retinal degeneration involves neuroinflammation, and pro-inflammatory cytokines/chemokines are markedly increased in the eyes of patients with retinitis pigmentosa (RP). In this study, we investigated the changes of serum cytokines/chemokines in RP, and their relationships with visual parameters. Methods Forty-five consecutive patients with typical RP aged 20 to −39 years and 28 age-matched and gender-matched controls were included. Fifteen cytokines (interleukin [IL]-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, IL-13, 1L-15, IL-17, IL-23, interferon [IFN]-γ, and tumor necrosis factor [TNF]-α, TNF-β) and 9 chemokines (eotaxin, growth-related oncogene [GRO]-α, I-309, IL-8, IFN-γ-inducible protein [IP]-10, monocyte chemotactic protein [MCP]-1, MCP-2, regulated activation normal T-cell expressed and secreted [RANTES], and thymus and activated regulated chemokine [TARC]) in the serum were simultaneously measured by a multiplexed immunoarray (Q-Plex). Relationships between these cytokines/chemokines and indices of central vision, such as visual acuity (VA), the values of static perimetry tests (Humphrey Field analyzer, the central 10-2 program), and optical coherence tomography measures were analyzed in the patients with RP. Results Among the 15 cytokines and 9 chemokines, serum IL-8 and RANTES levels were significantly increased in patients with RP compared with controls (IL-8: P < 0.0001; RANTES: P < 0.0001). Among the elevated cytokines/chemokines, the levels of IL-8 were negatively correlated with VA (ρ = 0.3596 and P = 0.0165), and the average retinal sensitivity of four central points (ρ = −0.3691 and P = 0.0291), and 12 central points ( ρ = −0.3491 and P = 0.0398), as well as the central subfield thickness ( ρ = −0.3961 and P = 0.0094), and ellipsoid zone width ( ρ = −0.3841 and P = 0.0120). Conclusions Peripheral inflammatory response may be activated and serum IL-8 levels are associated with central vision in patients with RP.

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“…A comprehensive measurement of inflammatory cytokines and chemokines in the aqueous humor and vitreous of the eyes of RP patients using multiplex enzyme-linked immunosorbent assay showed that IL-6, IL-8, and MCP-1 are elevated in the aqueous humor of RP patients, and that a greater variety of molecules (e.g., IL-1β, IL2, IL-4, IL-6, IL-8, IL-10, IFN-γ, MCP-1) are increased in the vitreous with more significant fold changes ( 121 ). Lu et al also conducted multiple cytokine analyses and observed increased IL-6, IL-8, and MCP-1 levels and increased extracellular matrix-related proteins such as matrix metalloproteinases ( 127 ).…”

Section: Retinitis Pigmentosamentioning

confidence: 99%

New Insights Into Immunological Therapy for Retinal Disorders

et al. 2020

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In the twentieth century, a conspicuous lack of effective treatment strategies existed for managing several retinal disorders, including age-related macular degeneration; diabetic retinopathy (DR); retinopathy of prematurity (ROP); retinitis pigmentosa (RP); uveitis, including Behçet's disease; and vitreoretinal lymphoma (VRL). However, in the first decade of this century, advances in biomedicine have provided new treatment strategies in the field of ophthalmology, particularly biologics that target vascular endothelial growth factor or tumor necrosis factor (TNF)-α. Furthermore, clinical trials on gene therapy specifically for patients with autosomal recessive or X-linked RP have commenced. The overall survival rates of patients with VRL have improved, owing to earlier diagnoses and better treatment strategies. However, some unresolved problems remain such as primary or secondary non-response to biologics or chemotherapy, and the lack of adequate strategies for treating most RP patients. In this review, we provide an overview of the immunological mechanisms of the eye under normal conditions and in several retinal disorders, including uveitis, DR, ROP, RP, and VRL. In addition, we discuss recent studies that describe the inflammatory responses that occur during the course of these retinal disorders to provide new insights into their diagnosis and treatment.

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Multiple cytokine analyses of aqueous humor from the patients with retinitis pigmentosa

Cited by 30 publications

References 51 publications

Importance of Autoimmune Responses in Progression of Retinal Degeneration Initiated by Gene Mutations

Importance of Autoimmune Responses in Progression of Retinal Degeneration Initiated by Gene Mutations

Changes of Serum Inflammatory Molecules and Their Relationships with Visual Function in Retinitis Pigmentosa

New Insights Into Immunological Therapy for Retinal Disorders

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