Corneal Sensitivity and Dry Eye Symptoms in Patients with Keratoconus

Dienes, Lóránt; Kiss, Huba; Perényi, Kristóf; Nagy, Zoltán Zsolt; Acosta, M. Carmen; Gallar, Juana; Kovács, Illés

doi:10.1371/journal.pone.0141621

Cited by 29 publications

(25 citation statements)

References 50 publications

(50 reference statements)

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“…Hyperosmolarity is considered a biomarker for dry eyes in human 67 . Dry eye symptoms have been reported in KC patients [68][69][70] , thus reduced expression of AQP5 might account for dry eye symptoms in some KC patients. Extracellular matrix (ECM) regulatory pathways are important for corneal integrity; however dysregulation in these pathways have been reported with KC progression 24,45 .…”

Section: Mace Et Al Have Shown Anti-proliferative and Hyper-apoptotimentioning

confidence: 99%

Differential Expression of Coding and Long Noncoding RNAs in Keratoconus-affected Corneas

Khaled

Bykhovskaya

Yablonski

et al. 2018

Preprint

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PURPOSE Keratoconus (KC) is the most common corneal ectasia. We aimed to determine the differential expression of coding and long noncoding RNAs (lncRNAs) in human corneas affected with KC.METHODS 200ng total RNA from the corneas of 10 KC patients and 8 non-KC normal controls was used to prepare sequencing libraries with the SMARTer Stranded RNA-Seq kit after ribosomal RNA depletion. Paired-end 50bp sequences were generated using Illumina HiSeq 2500Sequencer. Differential analysis was done using TopHat and Cufflinks with a gene file from Ensembl and a lncRNA file from NONCODE. Pathway analysis was performed using WebGestalt.Using the expression level of differentially expressed coding and noncoding RNAs in each sample, we correlated their expression levels in KC and controls separately and identified significantly different correlations in KC against controls followed by visualization using Cytoscape. RESULTSUsing |fold change| ≥ 2 and a false discovery rate ≤ 0.05, we identified 436 coding RNAs and 584 lncRNAs with differential expression in the KC-affected corneas. Pathway analysis indicated the enrichment of genes involved in extracellular matrix, protein binding, glycosaminoglycan binding, and cell migration. Our correlation analysis identified 296 pairs of significant KC-specific correlations containing 117 coding genes enriched in functions related with cell migration/motility, extracellular space, cytokine response, and cell adhesion, suggesting the potential functions of these correlated lncRNAs, especially those with multiple pairs of correlations.CONCLUSIONS Our RNA-Seq based differential expression and correlation analyses have identified many potential KC contributing coding and noncoding RNAs.

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Section: Mace Et Al Have Shown Anti-proliferative and Hyper-apoptotimentioning

confidence: 99%

Differential Expression of Coding and Long Noncoding RNAs in Keratoconus-affected Corneas

Khaled

Bykhovskaya

Yablonski

et al. 2018

Preprint

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“…Keratoconus (KC), by definition, is a progressive disorder characterized by non-inflammatory corneal ectasia, stromal thinning that leads to corneal surface distortion [64,65]. The etiology of this disease remains unknown, although there is evidence base is genetic and can bond with systemic diseases and obvious factors like excessive rubbing of the eyes, and wearing contact lenses [64,65].…”

Section: Keratoconusmentioning

confidence: 99%

“…The etiology of this disease remains unknown, although there is evidence base is genetic and can bond with systemic diseases and obvious factors like excessive rubbing of the eyes, and wearing contact lenses [64,65]. The 80% of patients suffering from KC refers tired eye, irritation, and foreign body sensation, indicative elements of ocular dryness [64].…”

Section: Keratoconusmentioning

confidence: 99%

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Analysis of the Pathogenic Factors and Management of Dry Eye in Ocular Surface Disorders

Nebbioso¹,

Regno²,

Gharbiya³

et al. 2017

Preprint

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The alteration of the delicate balance that regulates the secretion and distribution of the tear film determines the dry eye (DE) syndrome, because the tear film represents the interface between the eye and the environment. Despite having a multifactorial origin, the main risk factors for the emergence of the ocular disease are female gender and advanced age. Peer-reviewed version available at Int. J. Mol. Sci. 2017, 18, 1764 doi:10.3390/ijms18081764 2 Likewise, morphological changes in several glands and in chemical composition of their secretions such as proteins, mucins, lipidics, aqueous tears, and salinity, are highly relevant factors to maintain a condition of good health of the ocular anterior segment. Another key factor of recurrence and onset of the disease is the presence of local and/or systemic infiammation that reflex on the ocular surface. However, it is one of the most commonly encountered disease in clinical practice and many other causes related to daily life and to lengthen the average life will contribute to the beginning. This review will consider how and what disorders of the ocular surface are responsible for a widespread pathology so. In the end, the most appropriate and new therapies will be briefly exposed according to the specific pathology.

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“…It presents with bulging of the cornea, giving the distinctive conical shaping observed. Although commonly described as noninflammatory, some studies have reported impaired tear secretion and DED in keratoconus patients [55,56]. Subsequently, a pilot study by Carracedo et al [57] investigated keratoconus patients (n = 15) for the presence of DED, using morphological assessment of goblet cells by IC.…”

Section: Dry Eye Disease and Other Ocular Conditions Keratoconusmentioning

confidence: 99%

Biomarkers of Ocular Surface Disease Using Impression Cytology

Hagan

2017

Biomark. Med.

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Impression cytology (IC) is a technique which permits the retrieval of the outermost layer of ocular surface cells via the use of various types of filters. It is a minimally invasive method of evaluating human conjunctival epithelial cell morphology in the diagnosis of dry eye disease, a common and distressing disorder associated with ageing, contact lens wear, autoimmune disorders and refractive (LASIK) surgery. IC may also be utilized in the diagnosis of other ocular diseases, such as keratoconus and thyroid orbitopathy. More recently, IC has been utilized for the subsequent investigation of gene and protein expression of conjunctival cells in order to identify novel diagnostic biomarkers and to further our understanding of the mechanisms underlying ocular surface disease. This review will therefore examine the literature concerning the role of IC in identifying cellular markers of eye disease, systemic diseases with ocular involvement and potential novel therapeutic targets. Impression cytology (IC) is a minimally invasive method of evaluating human ocular surface cells and is considered as the 'gold standard' technique for assessing cell morphology. Introduced by Thatcher et al. [1] and Egbert et al. [2], IC is an easy-to-use technique of directly retrieving (mainly conjunctival) cells, using various filter types which are gently applied to exposed (interpalpebral) conjunctival surfaces. The filters used include cellulose acetate [3], polycarbonate (Biopore, Millipore UK Ltd, Watford, UK) [4], nitrocellulose [5] or polyethersulfone (PES) [6] which are gently applied to exposed (interpalpebral) conjunctival surfaces. Recently, a more standardized tool for IC sampling has been introduced (Figures 1 & 2). The Eyeprim is a new single-use PES filter sampling medical device for retrieval of conjunctival cells (Opia Technologies, France) and a recent study by Lopez-Miguel et al. [7] performed an analysis of this tool versus the traditional IC method (PES). On a cohort of 20 healthy individuals, they extracted and compared RNA from both devices and found no significant differences in the mean yield (p ≥ 0.45), the total RNA amount (μg), or the amount normalized to membrane area [7]. Although an earlier study of the Eyeprim [8], suggested that it recovered more cells than traditional IC, Lopez-Miguel et al. [7] did not observe differences in the RNA collected between this device and PES.Historically, IC has been used to analyze pathological changes to conjunctival cells for indicators of squamous metaplasia in ocular surface disease (OSD) [9]. More recently, however, researchers have used IC to examine specific markers of inflammation, for example, HLA-DR, ICAM-1 and CD8 [10][11][12], and to examine novel biomarkers of dry eye disease (DED). The latter is performed in an attempt to understand the mechanisms underpinning DED pathophysiology and is now feasible, due to vast improvements in the assay sensitivities for gene and protein examination [13]. As a result, IC membranes can be subsequently analyzed using techniq...

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Corneal Sensitivity and Dry Eye Symptoms in Patients with Keratoconus

Cited by 29 publications

References 50 publications

Differential Expression of Coding and Long Noncoding RNAs in Keratoconus-affected Corneas

Differential Expression of Coding and Long Noncoding RNAs in Keratoconus-affected Corneas

Analysis of the Pathogenic Factors and Management of Dry Eye in Ocular Surface Disorders

Biomarkers of Ocular Surface Disease Using Impression Cytology

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