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Angiogenin, FGF-?, and IL-36? have higher expression levels in aqueous humor of nAMD patients in comparison to cataract patients.

ABSTRACT: BACKGROUND:Numerous cytokines have been proven to participate in the pathogenesis of neovascular age-related macular degeneration (nAMD). The present study aimed to investigate the aqueous humor cytokine expression profile in nAMD patients before and after ranibizumab treatments in comparison to cataract patients. METHODS:This prospective study included 20 treatment-naïve nAMD eyes of 20 patients who received three consecutive monthly injections of ranibizumab. Aqueous humor samples were collected before the first (baseline), second (1?month later), and third (2?months later) injections. Controls were 20 age- and gender-matched cataract patients without any other ocular disease. The aqueous concentrations of 28 cytokines were measured using a multiplex bead assay. Central macular thickness (CMT) and maximum retinal thickness (MRT)-3?mm were measured by spectral domain optical coherence tomography (SD-OCT). The greatest linear diameter (GLD) was measured by fundus fluorescein angiography (FA). RESULTS:Three cytokines in aqueous humor, including angiogenin, interleukin-36? (IL-36?), and fibroblast growth factor-acidic (FGF-?) were significantly higher in nAMD patients in comparison to cataract patients, both before and after two consecutive monthly ranibizumab injections. Compared with the nAMD patients' basal levels, two consecutive monthly ranibizumab injections effectively reduced the aqueous concentrations of VEGF-A and placental growth factor (PlGF), as well as the values of CMT, MRT-3?mm, and GLD. CONCLUSIONS:Angiogenin, IL-36?, and FGF-? have higher expression levels in nAMD patients in comparison to cataract patients, both before and after 2?months of ranibizumab therapy. These cytokines may have correlations with the pathogenesis of nAMD.

SUBMITTER: Chen K

PROVIDER: S-EPMC7592502 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Angiogenin, FGF-α, and IL-36β have higher expression levels in aqueous humor of nAMD patients in comparison to cataract patients.

Chen Kailin K Xu Wen W Zheng Jiao J Shen Yupeng Y Ma Jian J Chen Zhiqing Z

BMC ophthalmology 20201028 1

<h4>Background</h4>Numerous cytokines have been proven to participate in the pathogenesis of neovascular age-related macular degeneration (nAMD). The present study aimed to investigate the aqueous humor cytokine expression profile in nAMD patients before and after ranibizumab treatments in comparison to cataract patients.<h4>Methods</h4>This prospective study included 20 treatment-naïve nAMD eyes of 20 patients who received three consecutive monthly injections of ranibizumab. Aqueous humor sampl ...[more]

PMID: 33115414

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Project description:PurposeTo investigate the change in cytokine microenvironment of the aqueous humor (AH) after surgery in children with congenital or developmental cataracts.MethodsAH samples were obtained from 59 eyes diagnosed with a congenital or developmental cataract. Thirty-three of these eyes were aphakic following previous cataract surgery and were scheduled for secondary intraocular lens (IOL) implantation. Additionally, AH samples from 26 eyes that had not undergone surgery were taken. AH samples were then analyzed for 16 different inflammatory immune mediators using multiplex bead immunoassays and enzyme-linked immunosorbent assay (ELISA).ResultsThe mean interval between secondary IOL implantation and original cataract surgery was 24.85 months (range, 9-60 months). Levels of IL-6, IP-10 (CXCL10), MCP-1 (CCL2), and IL-2 were significantly elevated in the AH of eyes after surgery compared to eyes that did not undergo surgery (P < 0.001, P = 0.047, P = 0.006, P = 0.012, respectively). There was significant correlation between the levels of TGF-β2 and intraocular pressure (IOP) in postsurgical and nonsurgical eyes (r = 0.532, P = 0.006; r = 0.57, P = 0.001). Postsurgical outcomes, such as iris adhesions, capsular fibrosis, and capsular contraction, were found not to be significantly associated with cytokine levels in the AH after surgery; however, IL-6 levels in capsular exposure eyes were significantly higher than those in cortical closure eyes (P = 0.023).ConclusionsTo our knowledge, this is the first study to report significantly increased proinflammatory cytokine levels in the AH after congenital cataract extraction in children. Our study also suggests that this proinflammatory state may be maintained for a prolonged period of time. Overall, these results give us insight into the relationship between the inflammatory cytokine microenvironment of the aqueous humor and potential long-term complications following congenital cataract surgery.Translational relevanceThe inflammatory cytokine microenvironment of the aqueous humor might help explain potential long-term complications after surgery in patients with congenital or developmental cataracts.

Project description:Purpose:The aim of this study is to investigate the age-correlation of oxidative stress (OS, assessed by the accumulative OS damage marker protein carbonyls) in aqueous humour (AH; together with protein concentration) and lens epithelial cells plus capsule (LECs/capsule) in patients with cataract (CAT), and also suffering from pseudoexfoliation syndrome (PEX), primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PXG). Methods:AH samples from 78 male/female patients (21, 20, 19 and 18 with CAT, PEX, PXG, and POAG, respectively), and LECs/capsule samples from 104 male/female patients (34, 32, 18, and 20 with CAT, PEX, PXG and POAG, respectively) were collected during phacoemulsification CAT surgery. Average protein carbonyl concentrations were measured in patients grouped in 5-year age intervals (ranging from 56-60 to 86-90). The non-overlapping age ranges and numbers of the tested subjects did not allow comparative follow up studies for the tested diseases. Results:There is an age-dependent increase of protein carbonyls in AH (nmol mg-1 protein and ml-1), and in the order CAT<PXG=~POAG<PEX and CAT<PEX=~POAG<PXG respectively. Moreover, protein concentration in AH accumulates in the order CAT<PEX<POAG<PXG but is not age-related. An age-dependent increase of protein carbonyls (nmol mg-1 protein) is also observed in LECs/capsule, and in the order CAT<PEX=~POAG<PXG. Conclusions:The present study shows for the first time an age-increased OS-induced protein damage (protein carbonyl formation) in the AH and LECs/capsule of CAT patients with PEX, POAG or PXG. The slow rate of change of protein carbonyls strongly suggests a long-term implication of OS in ocular disease pathogenesis. Additionally, protein concentration levels in the AH of CAT patients increase independently of age, and in same as with protein carbonyls increasing order levels for CAT<POAG<PXG in AH and LECs/capsule. This may suggest a protein cross-diffusion taking place between AH and LECs/capsule, most likely originating from PEX deposition and/or necrotic/apoptotic LECs/capsule. Moreover, the findings of the present study establish the use of protein carbonyls (together with a methodology for their more accurate quantification, which overcomes serious unreliability problems of past methods) as an age accumulative marker of OS damage, for future studies that investigate long-term OS involvement in pseudoexfoliative ocular disorders.

Dataset Information

Angiogenin, FGF-?, and IL-36? have higher expression levels in aqueous humor of nAMD patients in comparison to cataract patients.

Publications

Angiogenin, FGF-α, and IL-36β have higher expression levels in aqueous humor of nAMD patients in comparison to cataract patients.

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