Correlation of extracellular matrix‐related gene expression with objective Fuchs endothelial corneal dystrophy severity

Matthaei, Mario; Leitl, Christoph; Cursiefen, Claus; Heindl, Ludwig M.

doi:10.1111/ceo.13461

Cited by 4 publications

(5 citation statements)

References 5 publications

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“…We included 130 articles in this systematic review; 61 articles mentioned the diagnostic criteria for FECD, 3,6,13–71 whereas 99 described its severity classification. 3–6,14,16,17,21,22,25,29,31,33,37,39,41,42,44,45,50,51,53–55, 64–138…”

Section: Resultsmentioning

confidence: 99%

Systematic Review of the Diagnostic Criteria and Severity Classification for Fuchs Endothelial Corneal Dystrophy

Oie,

Yamaguchi,

Nishida

et al. 2023

Cornea

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Purpose: There are no defined diagnostic criteria and severity classification for Fuchs endothelial corneal dystrophy (FECD), which are required for objective standardized assessments. Therefore, we performed a systematic literature review of the current diagnosis and severity classification of FECD. Methods: We searched the Ovid MEDLINE and Web of Science databases for studies published until January 13, 2021. We excluded review articles, conference abstracts, editorials, case reports with <5 patients, and letters. Results: Among 468 articles identified, we excluded 173 and 165 articles in the first and second screenings, respectively. Among the 130 included articles, 61 (47%) and 99 (76%) mentioned the diagnostic criteria for FECD and described its severity classification, respectively. Regarding diagnosis, slitlamp microscope alone was the most frequently used device in 31 (51%) of 61 articles. Regarding diagnostic findings, corneal guttae alone was the most common parameter [adopted in 23 articles (38%)]. Regarding severity classification, slitlamp microscopes were used in 88 articles (89%). The original or modified Krachmer grading scale was used in 77 articles (78%), followed by Adami's classification in six (6%). Specular microscopes or Scheimpflug tomography were used in four articles (4%) and anterior segment optical coherence tomography in one (1%). Conclusions: FECD is globally diagnosed by the corneal guttae using slitlamp examination, and its severity is predominantly determined by the original or modified Krachmer grading scale. Objective severity grading using Scheimpflug or anterior segment optical coherence tomography can be applied in the future innovative therapies such as cell injection therapy or novel small molecules.

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Section: Resultsmentioning

confidence: 99%

Systematic Review of the Diagnostic Criteria and Severity Classification for Fuchs Endothelial Corneal Dystrophy

Oie,

Yamaguchi,

Nishida

et al. 2023

Cornea

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“… 12 Matthaei et al reported increased gene expression of FN , LAMC1 , COLIVA1 , and COLIIIA1 and demonstrated that their upregulation was followed by an abnormal deposition of the proteins encoded by these genes. 35 Cui et al observed an upregulation of FN1 and TNC genes in FECD ex vivo specimens, 36 and a recent transcriptome analysis identified FN1 , SPP1 , and COL6A2 as the top upregulated genes in FECD ex vivo specimens. 37 Herein, we confirmed the upregulation of FN1 , TNC , and SPP1 in FECD .…”

Section: Discussionmentioning

confidence: 98%

“…ECM gene deregulation in late-stage FECD specimens has been previously studied. 12 , 35 Weller et al identified several collagen genes ( COLIV , COLIA1 , and COLIIIA1), glycoproteins (FN1 and LAMA2 ), integrins ( ITGA1 , ITGA3 , ITGA4 , ITGB1 , and ITGB3 ) , metalloproteinases and their inhibitors (MMP10 , MMP14 , and TIMP1 ), and apolipoproteins ( CLU ) as upregulated in FECD specimens. The protein expression of some of them, such as clusterin and type III collagen, has been confirmed on FECD DMs.…”

Section: Discussionmentioning

confidence: 99%

Expression and Impact of Fibronectin, Tenascin-C, Osteopontin, and Type XIV Collagen in Fuchs Endothelial Corneal Dystrophy

Tchatchouang,

Brunette,

Rochette

et al. 2024

Invest. Ophthalmol. Vis. Sci.

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Purpose Fuchs endothelial corneal dystrophy (FECD) is characterized by Descemet's membrane (DM) abnormalities, namely an increased thickness and a progressive appearance of guttae and fibrillar membranes. The goal of this study was to identify abnormal extracellular matrix (ECM) proteins expressed in FECD DMs and to evaluate their impact on cell adhesion and migration. Methods Gene expression profiles from in vitro (GSE112039) and ex vivo (GSE74123) healthy and FECD corneal endothelial cells were analyzed to identify deregulated matrisome genes. Healthy and end-stage FECD DMs were fixed and analyzed for guttae size and height. Immunostaining of fibronectin, tenascin-C, osteopontin, and type XIV collagen was performed on ex vivo specimens, as well as on tissue-engineered corneal endothelium reconstructed using healthy and FECD cells. An analysis of ECM protein expression according to guttae and fibrillar membrane was performed using immunofluorescent staining and phase contrast microscopy. Finally, cell adhesion was evaluated on fibronectin, tenascin-C, and osteopontin, and cell migration was studied on fibronectin and tenascin-C. Results SPP1 (osteopontin), FN1 (fibronectin), and TNC (tenascin-C) genes were upregulated in FECD ex vivo cells, and SSP1 was upregulated in both in vitro and ex vivo FECD conditions. Osteopontin, fibronectin, tenascin-C, and type XIV collagen were expressed in FECD specimens, with differences in their location. Corneal endothelial cell adhesion was not significantly affected by fibronectin or tenascin-C but was decreased by osteopontin. The combination of fibronectin and tenascin-C significantly increased cell migration. Conclusions This study highlights new abnormal ECM components in FECD, suggests a certain chronology in their deposition, and demonstrates their impact on cell behavior.

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“…Matthaei et al 9 published a small, but novel translational research study that used corneal endothelial samples sourced from patients with Fuchs endothelial dystrophy at the time of Descemet's membrane epithelial keratoplasty. They studied expression of extracellular matrix (ECM) molecules and showed that expression levels correlated positively with corneal oedema, which was quantified as a corneal central‐to‐peripheral thickness ratio at 3.5 mm.…”

mentioning

confidence: 99%

Ophthalmology Letterbox

Smith

2021

Clinical Exper Ophthalmology

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Correlation of extracellular matrix‐related gene expression with objective Fuchs endothelial corneal dystrophy severity

Cited by 4 publications

References 5 publications

Systematic Review of the Diagnostic Criteria and Severity Classification for Fuchs Endothelial Corneal Dystrophy

Systematic Review of the Diagnostic Criteria and Severity Classification for Fuchs Endothelial Corneal Dystrophy

Expression and Impact of Fibronectin, Tenascin-C, Osteopontin, and Type XIV Collagen in Fuchs Endothelial Corneal Dystrophy

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