Corneal Clouding: An Infrequent Ophthalmic Manifestation of Mitochondrial Disease

Lee, Hsiu-Fen; Lee, Huei-Jane; Chi, Ching‐Shiang; Tsai, Chi-Ren; Chang, Patricia Chuen-Tsuei

doi:10.1016/j.pediatrneurol.2005.12.002

Cited by 6 publications

(6 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, corneal dystrophy is not a typical manifestation and only sporadically reported. Lee et al [6] described a 9-year-old boy with corneal clouding and abnormalities on muscle biopsy confirming mitochondrial disease, and Gross-Jendroska et al [7] presented corneal clouding as an uncommon association with Kearns-Sayre syndrome. Our patient further supports the view that when present, the unusual pediatric finding of corneal clouding should raise suspicion of mitochondrial disease, particularly in a patient with multi-system involvement [6].…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, Niaudet et al report a patient with Pearson syndrome and proximal tubule dysfunction who was found to have the common 4,977 base pair deletion (nt 8,470-13,446) associated with mitochondrial DNA deletion syndromes, including Pearson, Kearns-Sayre, and progressive external ophthalmoplegia [6,10]. Our patient with corneal dystrophy and severe Fanconi syndrome has a larger, but overlapping, 7,424-base-pair deletion (nt 8,648-16,072) and thus may fall along the continuum of mitochondrial deletion disorders, exhibiting phenotypic similarities to Pearson and Kearns-Sayre syndromes.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

A mitochondrial DNA deletion presenting with corneal clouding and severe Fanconi syndrome

et al. 2012

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A mitochondrial DNA deletion presenting with corneal clouding and severe Fanconi syndrome

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Furthermore, mitochondrial defect was associated to inflammatory context and ROS production in ocular surface pathologies 8,15 . While mitochondrial dysfunction is associated with lens cloudiness 11,12 , no report has linked DOA to ocular surface defects. Despite these studies, the direct effect of mitochondrial disfunction on corneal biology remains elusive.…”

Section: Introductionmentioning

confidence: 99%

“…Inherited mitochondrial dysfunction is a key factor in the progression of Fuchs endothelial corneal dystrophy (FECD) and keratoconus [8][9][10] . Case reports have linked mitochondrial diseases to corneal cloudiness 11,12 , perforation 13 and edema 14 . Furthermore, mitochondrial defect was associated to inflammatory context and ROS production in ocular surface pathologies 8,15 .…”

Section: Introductionmentioning

confidence: 99%

Inherited mitochondrial dysfunction triggered by OPA1 mutation impacts the sensory innervation fibre identity, functionality and regenerative potential in the cornea

Meneux,

Feret,

Pernot

et al. 2024

Preprint

View full text Add to dashboard Cite

Mitochondrial dysfunctions are detrimental to organ metabolism. The cornea, transparent outmost layer of the eye, is prone to environmental aggressions, such as UV light, and therefore dependent on adequate mitochondrial function. While several reports have linked corneal defects to mitochondrial dysfunction, the impact of OPA1 mutation, known to induce such dysfunction, has never been studied in this context. We used the mouse line carrying OPA1delTTAG mutation to investigate its impact on corneal biology. To our surprise, neither the tear film composition nor the corneal epithelial transcriptomic signature were altered upon OPA1 mutation. However, when analyzing the corneal innervation, we discovered an undersensitivity of the cornea upon the mutation, but an increased innervation volume at 3 months. Furthermore, the fibre identity changed with a decrease of the SP+ axons. Finally, we demonstrated that the innervation regeneration was less efficient and less functional in OPA1+/- corneas. Altogether, our study describes the resilience of the corneal epithelial biology, reflecting the mitohormesis induced by the OPA1 mutation, and the adaptation of the corneal innervation to maintain its functionality despite its morphogenesis defects. These findings will participate to a better understanding of the mitochondrial dysfunction on peripheral innervation.

show abstract

“…For example, although corneal clouding occurs infrequently in infants and children, it is often associated with mucopolysaccharidoses or Fabry disease when it appears in these young individuals. Some of those cases have also exhibited abnormal mitochondria in muscle biopsies analyzed under light and electron microscopy, implying significant mitochondrial dysfunction [30]. Similarly, previous work on keratocornus (KC), a noninflammatory thinning disorder usually involving the central or inferior cornea, revealed that KC corneas exhibited more mtDNA damage than did normal corneas [31], suggesting that increased oxidative stress and compromised mtDNA integrity may be involved in KC pathogenesis [32].…”

Section: Introductionmentioning

confidence: 99%

Genetic Background and Climatic Droplet Keratopathy Incidence in a Mapuche Population from Argentina

et al. 2013

View full text Add to dashboard Cite

PurposeTo determine whether the incidence of and susceptibility to climatic droplet keratopathy (CDK), an acquired, often bilateral degenerative corneal disease, is influenced by the genetic background of the individuals who exhibit the disorder.MethodsTo determine whether the disease expression was influenced by the genetic ancestry of CDK cases in native Mapuche of the northwest area of Patagonia in Argentina, we examined mitochondrial DNA and Y-chromosome variation in 53 unrelated individuals. Twenty-nine of them were part of the CDK (patient) population, while 24 were part of the control group. The analysis revealed the maternal and paternal lineages that were present in the two study groups.ResultsThis analysis demonstrated that nearly all persons had a Native American mtDNA background, whereas 50% of the CDK group and 37% of the control group had Native American paternal ancestry, respectively. There was no significant difference in the frequencies of mtDNA haplogroups between the CDK patient and control groups. Although the Y-chromosome data revealed differences in specific haplogroup frequencies between these two groups, there was no statistically significant relationship between individual paternal genetic backgrounds and the incidence or stage of disease.ConclusionsThese results indicate a lack of correlation between genetic ancestry as represented by haploid genetic systems and the incidence of CDK in Mapuche populations. In addition, the mtDNA appears to play less of a role in CDK expression than for other complex diseases linked to bioenergetic processes. However, further analysis of the mtDNA genome sequence and other genes involved in corneal function may reveal the more precise role that mitochondria play in the expression of CDK.

show abstract

Corneal Clouding: An Infrequent Ophthalmic Manifestation of Mitochondrial Disease

Cited by 6 publications

References 10 publications

A mitochondrial DNA deletion presenting with corneal clouding and severe Fanconi syndrome

A mitochondrial DNA deletion presenting with corneal clouding and severe Fanconi syndrome

Inherited mitochondrial dysfunction triggered by OPA1 mutation impacts the sensory innervation fibre identity, functionality and regenerative potential in the cornea

Genetic Background and Climatic Droplet Keratopathy Incidence in a Mapuche Population from Argentina

Contact Info

Product

Resources

About