Systemic Associations with Keratoconus

Unni, P. Ambili; Lee, Hyunjoo J

doi:10.3390/life13061363

Cited by 5 publications

(5 citation statements)

References 126 publications

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“…In multiple studies, it has been found that the expression levels of IL1B, IL6, and TNF in the tear fluids or epithelial cells were significantly elevated in KC patients [ 23 , 31 ]. IL4, a central role in atopic diseases, was also an important risk factor for KC [ 48 ]. IL10 is another primarily anti-inflammatory cytokine.…”

Section: Discussionmentioning

confidence: 99%

The candidate proteins associated with keratoconus: A meta-analysis and bioinformatic analysis

Song,

et al. 2024

PLoS ONE

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Purpose Keratoconus (KC) is a multifactorial disorder. This study aimed to conduct a systematic meta-analysis to exclusively explore the candidate proteins associated with KC pathogenesis. Methods Relevant literature published in the last ten years in Pubmed, Web of Science, Cochrane, and Embase databases were searched. Protein expression data were presented as the standard mean difference (SMD) and 95% confidence intervals (CI). The meta-analysis is registered on PROSPERO, registration number CRD42022332442 and was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement (PRISMA). GO and KEGG enrichment analysis were performed, as well as the miRNAs and chemicals targeting the candidate proteins were predicted. PPI was analyzed to screen the hub proteins, and their expression was verified by RT-qPCR. Results A total of 21 studies were included in the meta-analysis, involving 346 normal eyes and 493 KC eyes. 18 deregulated proteins with significant SMD values were subjected to further analysis. In which, 7 proteins were up-regulated in KC compared with normal controls, including IL6 (SMD 1.54, 95%CI [0.85, 2.24]), IL1B (SMD 2.07, 95%CI [0.98, 3.16]), TNF (SMD 2.1, 95%CI [0.24, 3.96]), and MMP9 (SMD 1.96, 95%CI [0.68, 3.24]). While 11 proteins were down-regulated in KC including LOX (SMD 2.54, 95%CI [-4.51, -0.57]). GO and KEGG analysis showed that the deregulated proteins were involved in inflammation, extracellular matrix (ECM) remodeling, and apoptosis. MMP9, IL6, LOX, TNF, and IL1B were regarded as hub proteins according to the PPI analysis, and their transcription changes in stromal fibroblasts of KC were consistent with the results of the meta-analysis. Moreover, 10 miRNAs and two natural polyphenols interacting with hub proteins were identified. Conclusion This study obtained 18 candidate proteins and demonstrated altered cytokine profiles, ECM remodeling, and apoptosis in KC patients through meta-analysis and bioinformatic analysis. It will provide biomarkers for further understanding of KC pathogenesis, and potential therapeutic targets for the drug treatment of KC.

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Section: Discussionmentioning

confidence: 99%

The candidate proteins associated with keratoconus: A meta-analysis and bioinformatic analysis

Song,

et al. 2024

PLoS ONE

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“…The pathophysiology of KC is a subject still under debate [38], with the inflammatory theory being the one that has been on the rise in recent times [39], especially due to its association with ocular rubbing [40]. However, much remains to be known since genetic factors, family associations, and systemic conditions have also been related to its development [38,41]. Moreover, the proteomic and transcriptomic analysis suggested dysregulations in oxidative stress, NRF2-regulated antioxidant programs, WNT-signaling, TGF-β, ECM, and matrix metalloproteinases as possible causes of KC [38].…”

Section: Discussionmentioning

confidence: 99%

Ocular Surface Microbiota in Naïve Keratoconus: A Multicenter Validation Study

Rocha-de-Lossada,

Mazzotta,

Gabrielli

et al. 2023

JCM

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In the field of Ophthalmology, the mNGS 16S rRNA sequencing method of studying the microbiota and ocular microbiome is gaining more and more weight in the scientific community. This study aims to characterize the ocular microbiota of patients diagnosed with keratoconus who have not undergone any prior surgical treatment using the mNGS 16S rRNA sequencing method. Samples of naïve keratoconus patients were collected with an eNAT with 1 mL of Liquid Amies Medium (Copan Brescia, Italy), and DNA was extracted and analyzed with 16S NGS. The microbiota analysis showed a relative abundance of microorganisms at the phylum level in each sample collected from 38 patients with KC and 167 healthy controls. A comparison between healthy control and keratoconus samples identified two genera unique to keratoconus, Pelomonas and Ralstonia. Our findings suggest that alterations in the microbiota may play a role in the complex scenario of KC development.

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“…The expression of Diagnostics 2024, 14, 707 2 of 17 collagens I and IV and of other structural proteins is reduced in KC patients [6]. Similar molecular changes happen in connective tissue diseases and a link between Ehlers-Danlos syndrome, Marfan's syndrome, osteogenesis imperfecta and mitral valve prolapse and KC has been proposed, although, in general, the scientific evidence is weak and few studies exist on this topic [7].…”

Section: Introductionmentioning

confidence: 99%

Reduced Retinal Blood Vessel Densities Measured by Optical Coherence Tomography Angiography in Keratoconus Patients Are Negatively Correlated with Keratoconus Severity

Leclaire,

Storp,

Lahme

et al. 2024

Diagnostics

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Keratoconus (KC) is the most common corneal ectasia. Optical coherence tomography angiography (OCT-A) is a relatively new non-invasive imaging technique that allows the visualization and quantification of retinal and choriocapillary blood vessels. The aim of this study is to assess retinal and choriocapillary vessel density (VD) differences between KC patients and healthy controls and to investigate correlations between VD and KC severity. Fifty-two eyes were included in this exploratory study: twenty-six eyes from 26 KC patients and twenty-six eyes from 26 age- and gender-matched healthy controls. All patients underwent Scheimpflug corneal topography with Pentacam, axis lengths measurement and optical coherence tomography angiography (OCT-A). The thinnest spot in corneal pachymetry, maximum K (Kmax) and KC severity indices from the Belin/Ambrósio enhanced ectasia display (BAD) were also assessed. There was a distinct reduction particularly in the retinal VD of the superficial capillary plexus (SCP). Correlation analyses showed strong and moderate negative correlations between the VD in the macular SCP and BAD KC scores and between the SCP VD and Kmax. There was no difference in retinal thickness between the KC and healthy controls. With this study, further evidence for altered VD measurements by OCT-A in KC patients is given. For the first time, we demonstrated negative correlations between BAD KC scores and retinal blood vessel alterations. A major limitation of the study is the relatively small sample size. Since an artefactual reduction of the quantitative OCT-A measurements due to irregular corneal topography in KC must be assumed, it remains to be investigated whether there are also actual changes in the retinal microcirculation in KC.

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Systemic Associations with Keratoconus

Cited by 5 publications

References 126 publications

The candidate proteins associated with keratoconus: A meta-analysis and bioinformatic analysis

The candidate proteins associated with keratoconus: A meta-analysis and bioinformatic analysis

Ocular Surface Microbiota in Naïve Keratoconus: A Multicenter Validation Study

Reduced Retinal Blood Vessel Densities Measured by Optical Coherence Tomography Angiography in Keratoconus Patients Are Negatively Correlated with Keratoconus Severity

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