motion-acuity-test-for-visual-field-acuity-measurement-with-motion

Motion-Acuity Test for Visual Field Acuity Measurement with Motion-Defined Shapes

The standard visual acuity measurements rely on stationary stimuli, either letters (Snellen charts), vertical lines (vernier acuity) or grating charts, ...

erratum-motion-acuity-test-for-visual-field-acuity-measurement-with

Erratum: Motion-Acuity Test for Visual Field Acuity Measurement with Motion-Defined Shapes

This corrects the article ...

Polish Academy of Sciences

Medical University of Warsaw

Keratoconus (KTCN), a non-inflammatory corneal disorder characterized by stromal thinning, represents a major cause of corneal transplantations. Genetic and environmental factors have a role in the etiology of this complex disease. Previously reported linkage analysis revealed that chromosomal region 13q32 is likely to contain causative gene(s) for familial KTCN. Consequently, we have chosen eight positional candidate genes in this region: MBNL1, IPO5, FARP1, RNF113B, STK24, DOCK9, ZIC5 and ZIC2, and sequenced all of them in 51 individuals from Ecuadorian KTCN families and 105 matching controls. The mutation screening identified one mutation and three sequence variants showing 100% segregation under a dominant model with KTCN phenotype in one large Ecuadorian family. These substitutions were found in three different genes: c.2262A>C (p.Gln754His) and c.720+43A>G in DOCK9; c.2377-132A>C in IPO5 and c.1053+29G>C in STK24. PolyPhen analyses predicted that c.2262A>C (Gln754His) is possibly damaging for the protein function and structure. Our results suggest that c.2262A>C (p.Gln754His) mutation in DOCK9 may contribute to the KTCN phenotype in the large KTCN-014 family.

Novel mutation and three other sequence variants segregating with phenotype at keratoconus 13q32 susceptibility locus.

To test the possibility that some chronic systemic maladies not directly related to the function of the eye may significantly and permanently disturb corneal metabolism.

Impact of donor health on corneal biochemistry--an unexpected caveat from a pilot study.

To estimate and compare cerebral cortex thickness in patients with unilateral end-stage glaucoma with that of age-matched individuals with unaffected vision.

Mapping cortical thickness of the patients with unilateral end-stage open angle glaucoma on planar cerebral cortex maps.

Keratoconus (KTCN) is a degenerative disorder of the eye that results in the conical shape and thinning of the cornea and is a leading cause for corneal transplantations. A number of studies suggest that genetic factors play a role in KTCN etiology. Some candidate gene variants have recently been shown to be associated with KTCN. The purpose of our study was to verify the role of VSX1, TGFBI, DOCK9, IPO5, and STK24 sequence variants in Polish KTCN patients.

Molecular Screening of Keratoconus Susceptibility Sequence Variants in VSX1, TGFBI, DOCK9, STK24, and IPO5 Genes in Polish Patients and Novel TGFBI Variant Identification.

Keratoconus (KTCN) is a degenerative disorder characterized by stromal thinning and protrusion of the cornea, resulting in severe impairment of visual function. A recent study proposed that rare heterozygous mutations in ZNF469 determine KTCN aetiology.

Evidence against ZNF469 being causative for keratoconus in Polish patients.

Keratoconus (KTCN, OMIM 148300) is a degenerative eye disorder characterized by progressive stromal thinning that leads to a conical shape of the cornea, resulting in optical aberrations and even loss of visual function. The biochemical background of the disease is poorly understood, which motivated us to perform RNA-Seq experiment, aimed at better characterizing the KTCN transcriptome and identification of long non-coding RNAs (lncRNAs) that might be involved in KTCN etiology. The in silico functional studies based on predicted lncRNA:RNA base-pairings led us to recognition of a number of lncRNAs possibly regulating genes with known or plausible links to KTCN. The lncRNA sequences and data regarding their predicted functions in controlling the RNA processing and stability are available for browse, search and download in KTCNlncDB (http://rhesus.amu.edu.pl/KTCNlncDB/), the first online platform devoted to KTCN transcriptome.Database URL: http://rhesus.amu.edu.pl/KTCNlncDB/.

KTCNlncDB-a first platform to investigate lncRNAs expressed in human keratoconus and non-keratoconus corneas.

To understand better the factors contributing to keratoconus (KTCN), we performed comprehensive transcriptome profiling of human KTCN corneas for the first time using an RNA-Seq approach. Twenty-five KTCN and 25 non-KTCN corneas were enrolled in this study. After RNA extraction, total RNA libraries were prepared and sequenced. The discovery RNA-Seq analysis (in eight KTCN and eight non-KTCN corneas) was conducted first, after which the replication RNA-Seq experiment was performed on a second set of samples (17 KTCN and 17 non-KTCN corneas). Over 82% of the genes and almost 75% of the transcripts detected as differentially expressed in KTCN and non-KTCN corneas were confirmed in the replication study using another set of samples. We used these differentially expressed genes to generate a network of KTCN-deregulated genes. We found an extensive disruption of collagen synthesis and maturation pathways, as well as downregulation of the core elements of the TGF-β, Hippo, and Wnt signaling pathways influencing corneal organization. This first comprehensive transcriptome profiling of human KTCN corneas points further to a complex etiology of KTCN.

Collagen synthesis disruption and downregulation of core elements of TGF-β, Hippo, and Wnt pathways in keratoconus corneas.

Keratoconus (KTCN) is a complex eye disorder resulting in loss of visual function. Its development is affected by genetic and environmental components. The aim of this study was to unravel the role of epigenetic factors in KTCN.

Multiple Differentially Methylated Regions Specific to Keratoconus Explain Known Keratoconus Linkage Loci.

Keratoconus (KTCN) is a protrusion and thinning of the cornea, resulting in loss of visual acuity. The etiology of KTCN remains unclear. The purpose of this study was to assess the potential involvement of new genetic variants in KTCN etiology based on both the genomic and transcriptomic findings recognized in the same corneal tissues.

Accumulation of sequence variants in genes of Wnt signaling and focal adhesion pathways in human corneas further explains their involvement in keratoconus.

Keratoconus (KTCN) is a progressive eye disease, characterized by changes in the shape and thickness of the cornea that results in loss of visual acuity. While numerous KTCN candidate genes have been identified, the genetic etiology of the disease remains undetermined. To further investigate and verify the contribution of particular genetic factors to KTCN, we assessed 45 candidate genes previously indicated as involved in KTCN etiology based on transcriptomic and genomic data.

Further evaluation of differential expression of keratoconus candidate genes in human corneas.

The ocular microbiome composition has only been partially characterized. Here, we used RNA-sequencing (RNA-Seq) data to assess microbial diversity in human corneal tissue. Additionally, conjunctival swab samples were examined to characterize ocular surface microbiota. Short RNA-Seq reads, obtained from a previous transcriptome study of 50 corneal tissues, were mapped to the human reference genome GRCh38 to remove sequences of human origin. The unmapped reads were then used for taxonomic classification by comparing them with known bacterial, archaeal, and viral sequences from public databases. The components of microbial communities were identified and characterized using both conventional microbiology and polymerase chain reaction (PCR) techniques in 36 conjunctival swabs. The majority of ocular samples examined by conventional and molecular techniques showed very similar microbial taxonomic profiles, with most of the microorganisms being classified into , , and  phyla. Only 50% of conjunctival samples exhibited bacterial growth. The PCR detection provided a broader overview of positive results for conjunctival materials. The RNA-Seq assessment revealed significant variability of the corneal microbial communities, including fastidious bacteria and viruses. The use of the combined techniques allowed for a comprehensive characterization of the eye microbiome's elements, especially in aspects of microbiota diversity.

Characterization of Ocular Surface Microbial Profiles Revealed Discrepancies between Conjunctival and Corneal Microbiota.

Mitochondrial DNA (mtDNA) abnormalities were previously found to be causative in the pathogenesis of various diseases. Here, comprehensive mitochondrial and nuclear sequence and transcript analyses, along with analyses of the methylation aspects of nuclear genes related to mitochondrial function, were performed in patients with keratoconus (KTCN) to evaluate their contribution to the KTCN pathogenesis.

Changes in Nuclear Gene Expression Related to Mitochondrial Function Affect Extracellular Matrix, Collagens, and Focal Adhesion in Keratoconus.

The first human corneal transplantation was performed in 1905 by Eduard Zirm in the Olomouc Eye Clinic, now Czech Republic. However, despite great advancements in microsurgical eye procedures, penetrating keratoplasty in high-risk patients (e.g., vascularized or inflamed corneal tissue, consecutive transplants) remains a challenge. The difficulty is mainly due to the risk of irreversible allograft rejection, as an ocular immune privilege in these patients is abolished and graft rejection is the main cause of corneal graft failure. Therefore, tailored immunosuppressive treatment based on immunological monitoring [e.g., donor-specific antibodies (DSA)] is considered one of the best strategies to prevent rejection in transplant recipients. Although there is indirect evidence on the mechanisms underlying antibody-mediated rejection, the impact of DSA on cornea transplantation remains unknown. Determining the role of pre-existing and/or de novo DSA could advance our understanding of corneal graft rejection mechanisms. This may help stratify the immunological risk of rejection, ultimately leading to personalized treatment for this group of transplant recipients.

Immunology and Donor-Specific Antibodies in Corneal Transplantation.

ALDH3A1 protein is important in maintaining corneal physiology and protecting the eye from UV damage. However, none of the genome-wide association studies has indicated that the  locus is associated with keratoconus. In this study, we examined the potential role of  variants as risk factors for keratoconus incidence and severity in a large group of Polish keratoconus patients.

ArticleTotal : 2	Year
Publication title Cited by 3	2024
Publication title	2024

Article	Year
Novel mutation and three other sequence variants segregating with phenotype at keratoconus 13q32 susceptibility locus. European journal of human genetics : EJHG\| PubMed ID: 22045297	2012
Impact of donor health on corneal biochemistry--an unexpected caveat from a pilot study. Annals of transplantation\| PubMed ID: 24621788	2014
Mapping cortical thickness of the patients with unilateral end-stage open angle glaucoma on planar cerebral cortex maps. PloS one\| PubMed ID: 24709970	2014
Molecular Screening of Keratoconus Susceptibility Sequence Variants in VSX1, TGFBI, DOCK9, STK24, and IPO5 Genes in Polish Patients and Novel TGFBI Variant Identification. Ophthalmic genetics\| PubMed ID: 24940934	2016
Evidence against ZNF469 being causative for keratoconus in Polish patients. Acta ophthalmologica\| PubMed ID: 26806788	2016
KTCNlncDB-a first platform to investigate lncRNAs expressed in human keratoconus and non-keratoconus corneas. Database : the journal of biological databases and curation\| PubMed ID: 28077570	2017
Collagen synthesis disruption and downregulation of core elements of TGF-β, Hippo, and Wnt pathways in keratoconus corneas. European journal of human genetics : EJHG\| PubMed ID: 28145428	2017
Multiple Differentially Methylated Regions Specific to Keratoconus Explain Known Keratoconus Linkage Loci. Investigative ophthalmology & visual science\| PubMed ID: 30994860	2019
Accumulation of sequence variants in genes of Wnt signaling and focal adhesion pathways in human corneas further explains their involvement in keratoconus. PeerJ\| PubMed ID: 32328353	2020
Further evaluation of differential expression of keratoconus candidate genes in human corneas. PeerJ\| PubMed ID: 32879808	2020
Characterization of Ocular Surface Microbial Profiles Revealed Discrepancies between Conjunctival and Corneal Microbiota. Pathogens (Basel, Switzerland)\| PubMed ID: 33808469	2021
Changes in Nuclear Gene Expression Related to Mitochondrial Function Affect Extracellular Matrix, Collagens, and Focal Adhesion in Keratoconus. Translational vision science & technology\| PubMed ID: 34478492	2021
Immunology and Donor-Specific Antibodies in Corneal Transplantation. Archivum immunologiae et therapiae experimentalis\| PubMed ID: 34741683	2021
Common Gene Variant Associated with Keratoconus Risk in the Polish Population. Journal of clinical medicine\| PubMed ID: 35011749	2021

Jacek Szaflik

Biography

JoVE Journal Publications

Other Publications