Keratoconus at a Molecular Level: A Review

Volatier, Thomas; Figueiredo, Francisco C; Connon, Che J.

doi:10.1002/ar.24090

Cited by 32 publications

(32 citation statements)

References 108 publications

(98 reference statements)

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“…The genetic variations found in these genes in different populations worldwide are predominantly single nucleotide polymorphisms, which in most cases have a low association with the disease and are considered controversial by several researchers [ 3 , 8 , 9 , 11 , 12 , 24 , 37 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

“…Keratoconus (KC) is an asymmetrically bilateral corneal dystrophy characterized by progressive thinning of the cornea, which becomes cone-shaped in a process called ectasia, with a prevalence of approximately 1 in 2000 people [1][2][3][4][5][6][7]. It is currently known that KC is a multifactorial disease, involving genetic, environmental, and behavioral factors and etiology remains poorly understood [3,[7][8][9][10][11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

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Absence of the c.169+50delTAAACAG mutation of SOD1 gene in a sample of keratoconus patients in Brazilian population

et al. 2020

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Objective: To determine the presence of the 7-bp deletion c.169+50delTAA ACA G in intron 2 of Superoxide Dismutase-1 gene in keratoconic patients from the State of São Paulo, Brazil, which promotes splicing variations, resulting in non-functional Superoxide Dismutase-1 antioxidant proteins, which may damage the corneal structure. Results: A group of 35 keratoconic patients, from whom 35 peripheral blood samples and 58 samples of corneal fragments were evaluated, and a control group of 89 individuals, from whom 41 blood samples and 149 samples of corneal fragments were collected. After the amplification of DNA fragments by polymerase chain reaction, mutational screening analysis was performed by enzymatic digestion, followed by direct sequencing. The absence of the 7-bp c.169+50delTAA ACA G mutation in intron 2 of Superoxide Dismutase-1 gene was detected in the analyzed subjects of the 2 groups, both in the cornea and peripheral blood samples. Then, according to our results, there is no involvement of c.169+50delTAA ACA G deletion in the pathogenesis of keratoconus in this population, once it was not detected. But we emphasize that studies involving this deletion must be continued in an attempt to elucidate this issue.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Absence of the c.169+50delTAAACAG mutation of SOD1 gene in a sample of keratoconus patients in Brazilian population

et al. 2020

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“…Collagenase has been approved by United States Food and Drug Administration (FDA) as an injection to improve the range of motion in joints affected by advanced Dupuytren's disease [14]. In the eye, collagenase was found to increase in patients with keratoconus [12,15,16] due to reduction of its inhibitor [17,18]. However, no ultrastructural or nanomechanical investigation has been conducted to show its activity on corneal tissues.…”

Section: Introductionmentioning

confidence: 99%

Nano-Scale Stiffness and Collagen Fibril Deterioration: Probing the Cornea Following Enzymatic Degradation Using Peakforce-QNM AFM

Kazaili

Al-Hindy

Madine

et al. 2021

Sensors

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Under physiological conditions, the cornea is exposed to various enzymes, some of them have digestive actions, such as amylase and collagenase that may change the ultrastructure (collagen morphology) and sequentially change the mechanical response of the cornea and distort vision, such as in keratoconus. This study investigates the ultrastructure and nanomechanical properties of porcine cornea following incubation with α-amylase and collagenase. Atomic force microscopy (AFM) was used to capture nanoscale topographical details of stromal collagen fibrils (diameter and D-periodicity) and calculate their elastic modulus. Samples were incubated with varying concentrations of α-amylase and collagenase (crude and purified). Dimethylmethylene blue (DMMB) assay was utilised to detect depleted glycosaminoglycans (GAGs) following incubation with amylase. Collagen fibril diameters were decreased following incubation with amylase, but not D-periodicity. Elastic modulus was gradually decreased with enzyme concentration in amylase-treated samples. Elastic modulus, diameter, and D-periodicity were greatly reduced in collagenase-treated samples. The effect of crude collagenase on corneal samples was more pronounced than purified collagenase. Amylase was found to deplete GAGs from the samples. This enzymatic treatment may help in answering some questions related to keratoconus, and possibly be used to build an empirical animal model of keratoconic corneas with different progression levels.

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“…This collection of manuscripts covers the current data on corneal structure, disease, inflammation, oxygen tension, cell communication through direct connections and secreting EVs. The leading article in this group is a review on the most common ectatic disease of the cornea, keratoconus (Volatier et al, 2020). Keratoconus is the thinning and stretching of the corneal stroma that is a unique transparent, highly organized collagen and proteoglycan ECM, with some thin fibroblast shaped cells called keratocytes.…”

mentioning

confidence: 99%

“…This article's introduction provides an excellent description of the corneal layers and their functions. This review explores how the relatively common disease, keratoconus, occurs by exploring the current knowledge of pathological signaling pathways in the cornea (Volatier et al, 2020). Another pathological problem, fibrosis, is addressed in the next article that uses the lens and cornea as model systems to not only understand fibrosis but also find new treatments to deter it developing in other organs (Menko et al, 2020).…”

mentioning

confidence: 99%

Extracellular matrix: The proteins that function throughout the body

Svoboda¹,

Gordon

2020

The Anatomical Record

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The idea and meetings that planned this issue focused on extracellular matrix (ECM) started over 4 years ago. The invitations were sent to investigators over 2 years ago and manuscripts have been submitted, reviewed, and edited since the summer and fall of 2018. Most of the manuscripts were published in early view in 2019, and we are thrilled to share the final collection. This volume contains 6 reviews, 13 original research papers, and 4 remembrances. Marion (Emmy) Gordon and I organized the articles into seven topic areas, including ECM structure, genetics, and development; cancer; vascular structures and development; inflammation and wound healing; collagen in special structures; cornea and other ocular tissues; and extracellular vesicles. Anat Rec, 303:1509Rec, 303: -1513Rec, 303: , 2020 This special issue of The Anatomical Record explores the many roles of extracellular matrix (ECM), highlighting the work of investigators that study subjects ranging from development, to gene expression, to how the cornea maintains transparency, to how cells use extracellular vesicles (EVs) to communicate. Without the ECM, students would have less anatomy to study because tissue organization, cartilage, bones, or blood vessels would not exist. Fortunately, ECM is in nearly all animals, including the most primitive. ECM can be used to study evolution, development, wound healing, cancer, angiogenesis, vasculogenesis, fibrosis, and cell-cell communication. Our bones, muscles, blood vessels, and other organs are built from and supported by ECM molecules, enabling our bodies to perform specific functions that give us great freedom to walk, talk, and see our world. ECM molecules do not act alone but are found in supramolecular structures that may include growth factors and soluble and insoluble proteins. The fibrillar components include collagens, laminins, elastin, and fibronectin, while the nonfibrillar components include growth factors, glycosaminoglycans, and proteoglycans. Cells that populate the ECM are either the cells that produce the matrix molecules or transient cells that preside in ECM for short periods of time to facilitate bodily functions and repair injured tissue. This issue is divided into seven topic sections, including ECM structure, genetics and development, cancer, vascular structures and development, inflammation and wound healing, collagen in special structures, cornea and other ocular tissues, and EVs.An exploration of the ECM ultrastructure (cover, Keene and Tufa, 2020) comparing traditional fixation and embedding to high-pressure freeze-substitution (HPFS) is the first contribution to the special issue. The HPFS

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Keratoconus at a Molecular Level: A Review

Cited by 32 publications

References 108 publications

Absence of the c.169+50delTAAACAG mutation of SOD1 gene in a sample of keratoconus patients in Brazilian population

Absence of the c.169+50delTAAACAG mutation of SOD1 gene in a sample of keratoconus patients in Brazilian population

Nano-Scale Stiffness and Collagen Fibril Deterioration: Probing the Cornea Following Enzymatic Degradation Using Peakforce-QNM AFM

Extracellular matrix: The proteins that function throughout the body

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