Review

Kok, Yee Onn; Tan, Grace Feng Ling; Loon, Seng Chee

doi:10.1097/ico.0b013e31820cd61d

Cited by 102 publications

(49 citation statements)

References 154 publications

(91 reference statements)

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“…It is a significant clinical problem worldwide, affecting both genders and all ethnicities [3, 4]. Owing to the limited availability of medical treatments, end-stage KC patients have to accept corneal transplantation.…”

Section: Introductionmentioning

confidence: 99%

Decreased Integrity, Content, and Increased Transcript Level of Mitochondrial DNA Are Associated with Keratoconus

Hao

Chen

et al. 2016

PLoS ONE

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Oxidative stress may play an important role in the pathogenesis of keratoconus (KC). Mitochondrial DNA (mtDNA) is involved in mitochondrial function, and the mtDNA content, integrity, and transcript level may affect the generation of reactive oxygen species (ROS) and be involved in the pathogenesis of KC. We designed a case-control study to research the relationship between KC and mtDNA integrity, content and transcription. One-hundred ninety-eight KC corneas and 106 normal corneas from Chinese patients were studied. Quantitative real-time PCR was used to measure the relative mtDNA content, transcript levels of mtDNA and related genes. Long-extension PCR was used to detect mtDNA damage. ROS, mitochondrial membrane potential and ATP were measured by respective assay kit, and Mito-Tracker Green was used to label the mitochondria. The relative mtDNA content of KC corneas was significantly lower than that of normal corneas (P = 9.19×10−24), possibly due to decreased expression of the mitochondrial transcription factor A (TFAM) gene (P = 3.26×10−3). In contrast, the transcript levels of mtDNA genes were significantly increased in KC corneas compared with normal corneas (NADH dehydrogenase subunit 1 [ND1]: P = 1.79×10−3; cytochrome c oxidase subunit 1 [COX1]: P = 1.54×10−3; NADH dehydrogenase subunit 1, [ND6]: P = 4.62×10−3). The latter may be the result of increased expression levels of mtDNA transcription-related genes mitochondrial RNA polymerase (POLRMT) (P = 2.55×10−4) and transcription factor B2 mitochondrial (TFB2M) (P = 7.88×10−5). KC corneas also had increased mtDNA damage (P = 3.63×10−10), higher ROS levels, and lower mitochondrial membrane potential and ATP levels compared with normal corneas. Decreased integrity, content and increased transcript level of mtDNA are associated with KC. These changes may affect the generation of ROS and play a role in the pathogenesis of KC.

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Section: Introductionmentioning

confidence: 99%

Decreased Integrity, Content, and Increased Transcript Level of Mitochondrial DNA Are Associated with Keratoconus

Hao

Chen

et al. 2016

PLoS ONE

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“…[2] Its etiopathogenesis is not well-known. Degeneration of cornea may be the result of increased proteolytic enzyme activity (acid phosphatase, acid esterase, cathepsin B, cathepsin G, cathepsin K, and trypsin-2) along with decreased proteinase inhibitors (alpha2-macroglobulin, alpha1-antiprotease) in the cornea.…”

Section: Discussionmentioning

confidence: 99%

“…Increased inflammatory markers and cytokines (IL-1, IL1R, IL-6, ICAM-1, VCAM- 1) have been documented in keratoconus, which may promote keratinocyte apoptosis. [2] Increased expression of pro-apoptotic protein secreted frizzled related protein-1 (SFRP- 1) and Fas-ligand has been documented in keratoconus. [2] Increased eye rubbing (associated with increased corneal inflammatory markers) along with contact lens use (non-gas permeable) are risk factors for keratoconus.…”

Section: Discussionmentioning

confidence: 99%

“…[2] Increased expression of pro-apoptotic protein secreted frizzled related protein-1 (SFRP- 1) and Fas-ligand has been documented in keratoconus. [2] Increased eye rubbing (associated with increased corneal inflammatory markers) along with contact lens use (non-gas permeable) are risk factors for keratoconus. Eye rubbing may also explain its increased occurrence in patients with atopy and asthma.…”

Section: Discussionmentioning

confidence: 99%

“…[1] Keratoconus is the most common ectatic corneal disorder characterized by conical shape of cornea due to thinning of cornea as a result of degeneration, usually bilateral, leading to severe myopia and astigmatism. [2] The association of adrenal myelolipoma with keratoconus has not been reported previously.…”

Section: Introductionmentioning

confidence: 99%

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