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Novel Corneal Protein Biomarker Candidates Reveal Iron Metabolic Disturbance in High Myopia Eyes

ABSTRACT: Myopia is a major public health concern with increasing global prevalence and is the leading cause of vision loss and complications. The potential role of the cornea, a substantial component of refractive power and the protective fortress of the eye, has been underestimated in the development of myopia. Our study acquired corneal stroma tissues from myopic patients undergoing femtosecond laser-assisted small incision lenticule extraction (SMILE) surgery and investigated the differential expression of circulating proteins between subjects with low and high myopia by means of high-throughput proteomic approaches—the quantitative tandem mass tag (TMT) labeling method and parallel reaction monitoring (PRM) validation. Across all corneal stroma tissue samples, a total of 2,455 proteins were identified qualitatively and quantitatively, 103 of which were differentially expressed between those with low and high myopia. The differentially abundant proteins (DAPs) between the groups of stroma samples mostly demonstrated catalytic activity and molecular function regulator and transporter activity and participated in metabolic processes, biological regulation, response to stimulus, and so forth. Pathway enrichment showed that mineral absorption, ferroptosis, and HIF-1 signaling pathways were activated in the human myopic cornea. Furthermore, TMT analysis and PRM validation revealed that the expression of ferritin light chain (FTL, P02792) and ferritin heavy chain (FTH1, P02794) was negatively associated with myopia development, while the expression of serotransferrin (TF, P02787) was positively related to myopia status. Overall, our results indicated that subjects with low and high myopia could have different proteomic profiles or signatures in the cornea. These findings revealed disturbances in iron metabolism and corneal oxidative stress in the more myopic eyes. Iron metabolic proteins could serve as an essential modulator in the pathogenesis of myopia.

SUBMITTER: Chen J

PROVIDER: S-EPMC8517150 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundTo compare the corneal biomechanical changes after small incision lenticule extraction (SMILE) and femtosecond laser-assisted in situ keratomileusis (FS-LASIK) with the same programmed optical zone (POZ) and similar refractive correction in patients with high myopia.MethodsIn this prospective comparative study of the contralateral eye, 50 patients with high myopia with the same POZ and similar refractive correction who underwent SMILE in one eye and FS-LASIK in the other eye. Corneal biomechanical parameters and central corneal thickness (CCT) were measured using a Corvis ST II. All the patients were evaluated during follow-up visits beyond one year. Additionally, the corneal volume (CV) of the 10-mm diameter region was measured using a Pentacam.ResultsAmbrosio relational thickness to the horizontal profile (ARTh) and stiffness parameter A1 (SP-A1) decreased significantly after SMILE and FS-LASIK, whereas deformation amplitude ratio 2.0 mm (DA ratio 2.0 mm) and integrated radius (IR) increased significantly in both groups. The ARTh and SP-A1 were greater after SMILE than those after FS-LASIK at all the follow-up visits. In addition, there were greater amounts of CCT and CV after SMILE compared with that after FS-LASIK. Moreover, a positive correlation was found between ARTh and SP-A1 and postoperative CCT, while a negative correlation was found between IR and DA ratio 2.0 mm and postoperative CCT. A moderate correlation was observed between SP-A1 and CV after both SMILE and FS-LASIK, whereas there were no relationships between CV and ARTh, IR, or DA ratio 2.0 mm.ConclusionsSMILE had greater CCT, CV, ARTh, and SP-A1 than FS-LASIK in high myopia with the same POZ and similar refractive correction. Our results demonstrated that SMILE had lesser effect on corneal biomechanics than FS-LASIK in high myopia.KeywordsCorneal biomechanics; Corvis ST II; small incision lenticule extraction (SMILE); femtosecond laser-assisted in situ keratomileusis (FS-LASIK); high myopia.

Project description:BackgroundHigh myopia and cataracts are major causes of blindness in East and Southeast Asia. Corneal astigmatism is a major contributor to uncorrected poor vision after cataract surgery in patients with high myopia. The purpose of the present study was to evaluate the demographic characteristics and distribution of preoperative corneal astigmatism in Chinese cataract surgery candidates with high myopia.MethodsSwept-source optical coherence tomography-based optical biometry was performed preoperatively in consecutive cataract surgery candidates who were classified by axial length (AL) into a high myopia group (defined as AL ≥26.0 mm) and a control group (normal ALs). The demographics, ALs, and keratometry values were recorded.ResultsAmong 15,063 cataract surgery candidates (15,063 eyes), 1,921 patients (12.8%, 1,921 eyes) in the high myopia group and 11,880 patients (11,880 eyes) in the control group were enrolled. In the high myopia group, the mean age was 59.8±12.6 (standard deviation) years, which was younger than that in the control group (69.1±11.0 years, P<0.001). In the high myopia group, the mean corneal astigmatism was 1.20±0.83 dioptre (D), which was greater than that in the control group (0.93±0.69 D, P<0.001). In the high myopia group, 82.2% had corneal astigmatism ≥0.50 D, 51.4% ≥1.00 D, 27.4% ≥1.50 D and 14.4% ≥2.00 D, all of which were higher than the respective proportions in the control group (P<0.001 for all). In the high myopia group, 66.8% had moderate to high corneal astigmatism, and 42.8% had "with-the-rule" astigmatism, and both of these proportions were higher than the respective proportions in the control group (P<0.001 for both). In the high myopia group, corneal astigmatism tended to increase with increasing age (r =0.134, P<0.001) after the age of 50, which was consistent with the tendency in the control group.ConclusionsA significant burden of preoperative corneal astigmatism was observed in Chinese cataract surgery candidates with high myopia. Moderate to high corneal astigmatism was more common in highly myopic eyes than in normal AL eyes.

Project description:Pleural effusion is a common respiratory disease worldwide; however, rapid and accurate diagnoses of tuberculosis pleural effusion (TPE) and malignancy pleural effusion (MPE) remain challenging. Although extracellular vesicles (EVs) have been confirmed as promising sources of disease biomarkers, little is known about the metabolite compositions of its subpopulations and their roles in the diagnosis of pleural effusion. Here, we performed metabolomics and lipidomics analysis to investigate the metabolite characteristics of two EV subpopulations derived from pleural effusion by differential ultracentrifugation, namely large EVs (lEVs, pelleted at 20,000 × g) and small EVs (sEVs, pelleted at 110,000 × g), and assessed their metabolite differences between tuberculosis and malignancy. A total of 579 metabolites, including amino acids, acylcarnitines, organic acids, steroids, amides and various lipid species, were detected. The results showed that the metabolic profiles of lEVs and sEVs overlapped with and difference from each other but significantly differed from those of pleural effusion. Additionally, different type of vesicles and pleural effusion showed unique metabolic enrichments. Furthermore, lEVs displayed more significant and larger metabolic alterations between the tuberculosis and malignancy groups, and their differential metabolites were more closely related to clinical parameters than those of sEV. Finally, a panel of four biomarker candidates, including phenylalanine, leucine, phosphatidylcholine 35:0, and sphingomyelin 44:3, in pleural lEVs was defined based on the comprehensive discovery and validation workflow. This panel showed high performance for distinguishing TPE and MPE, particularly in patients with delayed or missed diagnosis, such as the area under the receiver-operating characteristic curve (AUC) >0.95 in both sets. We conducted comprehensive metabolic profiling analysis of EVs, and further explored the metabolic reprogramming of tuberculosis and malignancy at the level of metabolites in lEVs and sEVs, providing insight into the mechanism of pleural effusion, and identifying novel biomarkers for diagnosing TPE and MPE.

Project description:PurposeTo evaluate the early corneal remodeling and its influencing factors after Small incision lenticule extraction (SMILE) for moderate and high myopia.MethodsThis was a retrospective study. Pre- and post-operative (1 week and 1, 3, 6 months) corneal volume (CV), mean keratometry (Km), and corneal thickness (CT) were measured by Scheimpflug tomography. CT at the central, thinnest point, and on concentric circles of 2, 4, and 6 mm diameter was recorded to assess corneal thickness spatial profile (CTSP) and percentage of thickness increase (PTI) in the moderate and high myopia groups, and to explore possible influencing factors.ResultsAfter SMILE, the peripheral CT decreased in the moderate myopia group and central corneal thickness (CCT) increased in the high myopia group at 1 month compared to 1 week (all P < 0.05). The CV, Km and CT were significantly increased at 3 months compared to 1 month (all P < 0.05), but there was no significant change at 6 months compared to 3 months for both groups (all P > 0.05). Patients with high myopia showed greater corneal thickness changes (△CT) and higher PTI than moderate myopia (all P < 0.05). Regression analysis revealed that in addition to refraction, peripheral PTI was negatively correlated with CCT in the moderate myopia group (4 mm: β = -0.023, P = 0.001; 6 mm: β = -0.050, P < 0.001), as well as in the high myopia group (4 mm: β = -0.038, P < 0.001; 6 mm: β = -0.094, P < 0.001). Moreover, peripheral PTI in the moderate myopia group was negatively correlated with age (4 mm: β = -0.071, P = 0.003; 6 mm: β = -0.162, P < 0.001).ConclusionsAfter SMILE, the CV, Km, and CTSP showed dynamic changes in the early stage, which stabilized after 3 months. Compared to the moderate myopia group, the high myopia group experienced slower corneal stabilization. The change in PTI at 6 months after SMILE may be related to higher preoperative refraction, thinner CCT and younger age.

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Novel Corneal Protein Biomarker Candidates Reveal Iron Metabolic Disturbance in High Myopia Eyes

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