Distinct Aqueous Humour Cytokine Profiles of Patients with Pachychoroid Neovasculopathy and Neovascular Age-related Macular Degeneration

Terao, Nobuhiro; Koizumi, Hideki; Kojima, Kentaro; Yamagishi, Toshio; Yamamoto, Yuji; Yoshii, Kengo; Kitazawa, Koji; Hiraga, Asako; Toda, Munetoyo; Kinoshita, Shigeru; Sotozono, Chie; Hamuro, Junji

doi:10.1038/s41598-018-28484-w

Cited by 74 publications

(70 citation statements)

References 39 publications

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“…Although AH sampling is an invasive procedure, it is still accomplishable in humans in contrast to any of the tissue analyses, thereby supporting the diagnostic value of AH. The increased levels of pro-inflammatory cytokines in AH were previously found, not only in patients with pronounced intraocular inflammation (such as posterior uveitis), but also in individuals with AMD, diabetic retinopathy, macular edema, or glaucoma [39][40][41][42]. In the current study, we have demonstrated that the development of LIRD is accompanied by a chronic increase in the AH content of pro-inflammatory cytokine TNF-α.…”

Section: Discussionsupporting

confidence: 74%

“…Indeed, alterations in malondialdehyde concentration and total antioxidant activity were found in AH of patients with glaucoma and exfoliation syndrome, as well as in animals with intraocular inflammation [35][36][37][38]. Furthermore, the increased levels of pro-inflammatory cytokines characterize AH of patients with AMD, diabetic retinopathy, macular edema, and glaucoma [39][40][41][42]. Meanwhile, alterations in oxylipin content of AH that are associated with LIRD and other retinal degenerative diseases remain mostly uninvestigated.…”

Section: Introductionmentioning

confidence: 99%

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Mechanisms and Treatment of Light-Induced Retinal Degeneration-Associated Inflammation: Insights from Biochemical Profiling of the Aqueous Humor

Chistyakov

Baksheeva

Tiulina

et al. 2020

IJMS

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Ocular inflammation contributes to the pathogenesis of blind-causing retinal degenerative diseases, such as age-related macular degeneration (AMD) or photic maculopathy. Here, we report on inflammatory mechanisms that are associated with retinal degeneration induced by bright visible light, which were revealed while using a rabbit model. Histologically and electrophysiologically noticeable degeneration of the retina is preceded and accompanied by oxidative stress and inflammation, as evidenced by granulocyte infiltration and edema in this tissue, as well as the upregulation of total protein, pro-inflammatory cytokines, and oxidative stress markers in aqueous humor (AH). Consistently, quantitative lipidomic studies of AH elucidated increase in the concentration of arachidonic (AA) and docosahexaenoic (DHA) acids and lyso-platelet activating factor (lyso-PAF), together with pronounced oxidative and inflammatory alterations in content of lipid mediators oxylipins. These alterations include long-term elevation of prostaglandins, which are synthesized from AA via cyclooxygenase-dependent pathways, as well as a short burst of linoleic acid derivatives that can be produced by both enzymatic and non-enzymatic free radical-dependent mechanisms. The upregulation of all oxylipins is inhibited by the premedication of the eyes while using mitochondria-targeted antioxidant SkQ1, whereas the accumulation of prostaglandins and lyso-PAF can be specifically suppressed by topical treatment with cyclooxygenase inhibitor Nepafenac. Interestingly, the most prominent antioxidant and anti-inflammatory benefits and overall retinal protective effects are achieved by simultaneous administrating of both drugs indicating their synergistic action. Taken together, these findings provide a rationale for using a combination of mitochondria-targeted antioxidant and cyclooxygenase inhibitor for the treatment of inflammatory components of retinal degenerative diseases.

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Section: Discussionsupporting

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Mechanisms and Treatment of Light-Induced Retinal Degeneration-Associated Inflammation: Insights from Biochemical Profiling of the Aqueous Humor

Chistyakov

Baksheeva

Tiulina

et al. 2020

IJMS

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“…PNV ( Fig. 1) was diagnosed using the following criteria drawn from previous reports 2,3,11,27,28 : (1) type 1 CNV detected in either or both eyes; (2) no or only nonextensive drusen (total area 125 lm circle) or hard drusen ( 63 lm) in both eyes (Age-Related Eye Disease Study: Category 1, no AMD) 29 ; (3) CVH detected in the late phase of ICGA; (4) dilated choroidal vessels below the type 1 CNV detected by ICGA and SD-or SS-OCT; and (5) presence of CSC-or PPE-related RPE abnormalities independent of CNV lesions detected by FAF or a history of CSC.…”

Section: Diagnosis Of Acute Csc Chronic Csc and Pnvmentioning

confidence: 99%

“…2 Recently, we published the new findings that the cytokine profiles in aqueous humor (AH) of PNV and neovascular AMD are distinct, and that angiogenic factors and proinflammatory cytokines may play distinct roles in the pathogenesis of PNV and AMD. 11 It is well recognized that type 1 CNV occurs in eyes with long-term CSC, 12,13 but it can also occur in the absence of subretinal fluid. Some studies have speculated that the pathological progression of pachychoroid is conversion from acute CSC to chronic CSC or from PPE and eventually to PNV 14,15 ; however, not all patients with acute CSC develop chronic CSC, nor do all chronic CSC and PPE patients develop PNV.…”

mentioning

confidence: 99%

Association of Upregulated Angiogenic Cytokines With Choroidal Abnormalities in Chronic Central Serous Chorioretinopathy

Terao

Koizumi

Kojima

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. To clarify the distinct molecular pathogenesis of central serous chorioretinopathy (CSC) and pachychoroid neovasculopathy (PNV). METHODS. Aqueous humor (AH) was collected from 18 acute CSC, 20 chronic CSC, and 20 PNV patients. Concentrations of 30 cytokines in the AH were analyzed using a multiplex bead immunoassay, and the cytokine profiles were compared among these three groups of patients. The areas of choroidal vascular hyperpermeability (CVH) and choroidal thickness (CT), including measurement of the vascular layers, were investigated to analyze the features of choroidal abnormality in acute CSC, chronic CSC, and PNV. Additionally, associations between cytokine profiles and choroidal abnormalities were analyzed. RESULTS. Proinflammatory cytokines, IL-6 and IL-8 were significantly upregulated in the chronic CSC group compared with the acute CSC or PNV groups. Angiogenic cytokines and VEGF-A were upregulated at levels that almost reached significance along with disease progression from acute to chronic CSC, whereas the upregulation was not significant from chronic CSC to PNV. In the chronic CSC group, strong positive correlations were confirmed between VEGF-A and placental growth factor (PlGF) (r ¼ 0.75, P < 0.001) and IL-6 and VEGF-A (r ¼ 0.74, P < 0.001), and angiogenesis-related cytokines were positively correlated with the typical choroidal abnormalities, areas of CVH, mean CT, and mean large choroidal vessel layer thickness. However, there was no association between these choroidal abnormality parameters and AH cytokines in the PNV group. CONCLUSIONS. The results suggest that choroidal abnormalities in chronic CSC may be associated with upregulated angiogenesis.

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“…Two independent AMD specialists (M. Y. and H. H.) performed all of the diagnosis based on the criteria of pachychoroid spectrum disorders [18]. The supervising grader (N.…”

Section: Assessments Of Pachychoroid Spectrum and Choroidal Pachyvesselsmentioning

confidence: 99%

Clinical Implications of Pachyvessels in Polypoidal Choroidal Vasculopathy

Ijuin

Tsujinaka

Hirai

et al. 2019

Preprint

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Purpose: Polypoidal choroidal vasculopathy (PCV) is one of the disorders within the pachychoroid spectrum diseases. The presence of pachyvessels is one of the characteristics of pachychoroid disorders. However, the relationship between the presence of pachyvessels and the clinical characteristics of PCV eyes has not been determined. The purpose of this study was to determine the relationship between the presence of choroidal pachyvessels and the clinical characteristics of eyes with PCV.Methods: The medical records of patients who were diagnosed with PCV and were treatment-naïve were reviewed. Fluorescein and indocyanine green angiography, fundus photography, spectral domain optical coherence tomography (SD-OCT), and enhanced depth imaging OCT (EDI-OCT) were used to obtain images of the choroid. The PCV eyes were divided into two groups based on the presence or absence of pachyvessels and clinical features and subfoveal choroidal thickness (SFCT) were evaluated between the two groups.Results: Eighty-six eyes of 84 patients with PCV were evaluated. Pachyvessels were detected in 48 eyes (55.8％). The mean SFCT was 203.9 ± 83.9 μm in all 86 eyes, and it was significantly thinner in eyes with pachyvessels (+) than without pachyvessels (-) (183.2 ± 58.4 μm vs 230.2 ± 103.1 μm; P=0.01). The differences in the incidence of subretinal fluid, pigment epithelial detachments, and hemorrhages between the two groups were not significant. However, the PCV eyes in pachyvessels (+) group with hemorrhage had the thinnest choroid (P=0.047). The choroidal features of the fellow eyes were similar to those of the PCV affected eyes, that is, the fellow eyes in pachyvessels (+) group had pachyvessels and the fellow eyes in pachyvessels (-) group did not had pachyvessels. Conclusions: Pachyvessels were presented 55.8% in eyes with PCV, and these eyes had the thin SFCT. The presence of pachyvessels and attenuation of the inner choroid were probably due to the pathological changes in the eyes with PCV.

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Distinct Aqueous Humour Cytokine Profiles of Patients with Pachychoroid Neovasculopathy and Neovascular Age-related Macular Degeneration

Cited by 74 publications

References 39 publications

Mechanisms and Treatment of Light-Induced Retinal Degeneration-Associated Inflammation: Insights from Biochemical Profiling of the Aqueous Humor

Mechanisms and Treatment of Light-Induced Retinal Degeneration-Associated Inflammation: Insights from Biochemical Profiling of the Aqueous Humor

Association of Upregulated Angiogenic Cytokines With Choroidal Abnormalities in Chronic Central Serous Chorioretinopathy

Clinical Implications of Pachyvessels in Polypoidal Choroidal Vasculopathy

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