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In Vivo Confocal Microscopy Shows Alterations in Nerve Density and Dendritiform Cell Density in Fuchs' Endothelial Corneal Dystrophy.

ABSTRACT: PURPOSE:To evaluate corneal nerve and immune cell alterations in Fuchs' endothelial corneal dystrophy (FECD) and pseudophakic bullous keratopathy (PBK) by laser in vivo confocal microscopy (IVCM) as correlated to corneal sensation and endothelial cell loss. DESIGN:Prospective, cross-sectional, controlled study. METHODS:Thirty-three eyes with FECD were compared to 13 eyes with PBK and 17 normal age-matched control eyes at a tertiary referral center. FECD was classified into early (without edema) and late stage (with edema). Corneal IVCM and esthesiometry were performed. Corneal nerve and immune dendritiform cell (DC) alterations were evaluated and correlated to clinical parameters. RESULTS:FECD and PBK eyes showed significantly (P = .001) diminished total nerve length (11.5 ± 1.3 and 2.9 ± 0.7 mm/mm2) and number (8.8 ± 1.1 and 2.2 ± 0.4 n/frame), compared to controls (23.3 ± 8.1 mm/mm2 and 25.9 ± 1.3 n/frame). Decreased nerves corresponded to diminished sensation in FECD (4.9 ± 0.2 cm; R = 0.32; P = .045), compared to controls (5.9 ± 0.04 cm). Early- and late-stage FECD showed significantly reduced total nerve length (13.1 ± 1.4 and 9.9 ± 1.2 mm/mm2, respectively) and number (8.2 ± 2.5 and 6.5 ± 2.1 n/frame), compared to controls (P < .001). DC density was significantly increased in FECD (57.8 ± 10.4 cells/mm2; P = .01), but not in PBK (47.7 ± 11.6 cells/mm2; P = .60) compared to controls (22.5 ± 4.5 cells/mm2). A subset of early FECD patients (7/22) demonstrated very high DC density (>100/mm2). CONCLUSION:IVCM demonstrates profound diminishment of subbasal corneal nerves in early- and late-stage FECD and in PBK, correlating to decreased sensation. Increased DC density in early FECD demonstrates potential subclinical inflammation. The data suggest that reduction in subbasal nerves and increased immune activation may play a role in the pathophysiology of FECD.

SUBMITTER: Aggarwal S

PROVIDER: S-EPMC6420962 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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In Vivo Confocal Microscopy Shows Alterations in Nerve Density and Dendritiform Cell Density in Fuchs' Endothelial Corneal Dystrophy.

Aggarwal Shruti S Cavalcanti Bernardo M BM Cavalcanti Bernardo M BM Regali Laura L Cruzat Andrea A Trinidad Monique M Williams Candice C Jurkunas Ula V UV Hamrah Pedram P

American journal of ophthalmology 20180906

<h4>Purpose</h4>To evaluate corneal nerve and immune cell alterations in Fuchs' endothelial corneal dystrophy (FECD) and pseudophakic bullous keratopathy (PBK) by laser in vivo confocal microscopy (IVCM) as correlated to corneal sensation and endothelial cell loss.<h4>Design</h4>Prospective, cross-sectional, controlled study.<h4>Methods</h4>Thirty-three eyes with FECD were compared to 13 eyes with PBK and 17 normal age-matched control eyes at a tertiary referral center. FECD was classified into ...[more]

PMID: 30194928

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Project description:Fuchs’ endothelial corneal dystrophy (FECD) is a progressive vision impairing disease caused by thickening of Descemet’s membrane and gradual degeneration and loss of corneal endothelial cells. The aim of this study was to identify differentially expressed genes between FECD-affected and unaffected corneal endothelium to gain insight into the pathophysiological mechanisms underlying this disease. Microarray gene expression analysis was performed on total RNA from FECD-affected and unaffected corneal endothelium-Descemet’s membrane (CE-DM) specimens using the Illumina HumanHT-12 v3.0 expression array. RNA from pools of FECD-affected (n=3 per pool) and individual unaffected (n=3) specimens was used for comparison. Altered expression of a sub-set of differentially expressed genes was validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in independent specimens. Bioinformatics analysis was performed using InnateDB to reveal functional relationships among the differentially expressed genes and molecular pathways involved in the disease. A total of 16,513 genes were found expressed in the corneal endothelium of which 142 genes were differentially expressed between FECD-affected and unaffected endothelium (log2 fold-change ≥1.5, corrected p-value ≤0.05). Most of the genes were up-regulated (126) and a small proportion down-regulated (16) in affected corneal endothelium. Of the twelve genes prioritised for validation, differential expression of 10 genes, including those ranked 57th and 81st by significance validated by qRT-PCR (8 up-regulated and 2 downregulated, corrected p ≤0.05), one gene showed a trend for up-regulation in affected endothelium, consistent with the microarray analysis and another was up-regulated in an independent study indicating robustness of the differential expression dataset. Bioinformatic analysis revealed significant over-representation of differentially expressed genes in extracellular matrix reorganisation, cellular remodelling, immune response, and inflammation. Network analysis showed functional inter-relatedness of the majority of the dysregulated genes and revealed known direct functional relationships between 20 of the genes; many of these genes have roles in macrophage differentiation, phagocytosis and inflammation. This is the second report of microarray gene expression analysis in FECD. This study revealed a set of highly dysregulated genes in the corneal endothelium in FECD. More than a third of the dysregulated genes in the disease have been discovered for the first time and thus are novel. The dysregulated genes strongly suggest the presence of phagocytic cells, most likely immune cells, and inflammation in corneal endothelium in the disease. This study provides a molecular framework for delineating the mechanisms underlying these cellular processes in FECD.

Dataset Information

In Vivo Confocal Microscopy Shows Alterations in Nerve Density and Dendritiform Cell Density in Fuchs' Endothelial Corneal Dystrophy.

Publications

In Vivo Confocal Microscopy Shows Alterations in Nerve Density and Dendritiform Cell Density in Fuchs' Endothelial Corneal Dystrophy.

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