Mitochondrial Retinopathy

Birtel, Johannes; Landenberg, C. von; Gliem, Martin; Gliem, Carla; Reimann, Jens; Kunz, Wolfram S.; Herrmann, Philipp; Betz, Christian; Caswell, Richard; Nesbitt, Victoria; Kornblum, Cornelia; Issa, Peter Charbel

doi:10.1016/j.oret.2021.02.017

Cited by 37 publications

(26 citation statements)

References 53 publications

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“…This result motivates future studies in mitochondrial retinopathies. 79 Second, we show that band 2 is not a monolithic band in the periphery. Our suggestion of a rod-associated band 2b and cone-associated band 2a, which are not resolved by commercial NIR OCT instruments, would nicely explain findings that both rods and cones contribute to clinical band 2.…”

Section: Discussionmentioning

confidence: 66%

Visible Light Optical Coherence Tomography Reveals the Relationship of the Myoid and Ellipsoid to Band 2 in Humans

Srinivasan

Kho

Chauhan

2022

Trans. Vis. Sci. Tech.

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Purpose We employ visible light optical coherence tomography (OCT) to investigate the relationship between the myoid, ellipsoid, and band 2 in the living human retina. Rather than refute existing theories, we aim to reveal new bands and better delineate the structures at hand. Methods An upgraded spectral/Fourier domain visible light OCT prototype, with 1.0-µm axial resolution, imaged 13 eyes of 13 young adult human subjects (23–40 years old) without a history of ocular pathology. The external limiting membrane (band 1) and band 2 edges were segmented. Reflectivity was examined along the inner segment (IS), defined as extending from band 1 to the band 2 center, and within band 2 itself. Results Images highlight a nearly continuously resolved extrafoveal internal limiting membrane, the peripheral single-cell thick ganglion cell layer, and the peripheral photoreceptor axonal fiber layer, a peripheral division of band 2 into bands 2a and 2b, and a reflectivity-based division of the IS into “m” and “e” zones. Discussion Topography and transverse intensity variations of the outermost band 2b suggest an association with rods. The “m” and “e” zone border is consistent with the myoid–ellipsoid boundary, even recapitulating the well-documented distribution of mitochondria throughout the IS at the foveal center. Theories of outer retinal reflectivity in OCT must adequately explain these observations. Translational Relevance Findings support that band 2 does partially overlap with the ellipsoid in transversally averaged OCT images due to photoreceptor IS length dispersion but argue that the inner ellipsoid must be inner to band 2, as suggested by prior quantitative measurements.

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Section: Discussionmentioning

confidence: 66%

Visible Light Optical Coherence Tomography Reveals the Relationship of the Myoid and Ellipsoid to Band 2 in Humans

Srinivasan

Kho

Chauhan

2022

Trans. Vis. Sci. Tech.

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“…RP changes in mitochondrial disease can show considerable variability, but specific recurrent patterns allowed grouping into the following different types. In a recent survey of the genetic basis of 23 cases of mitochondrial retinopathy several interesting features have been reported [ 58 ].…”

Section: Genetic Heterogeneity In Mitochondrial Rpmentioning

confidence: 99%

“…Private mutations of mtDNA were present as m.3255G > A in MT-TL1, m.3244G > A in MT-TL1, m.1021T > C in MT-RNR1, m.9171A > G in MT-ATP6, m.8344A > G MERRF in MT-TK (MERRF stands for Myoclonus Epilepsy with Ragged-Red Fibres), and one case of multiple mtDNA deletions associated with a p.Ala192Val change in the protein encoded by the nuclear RRMB2 gene. Surprisingly, only one NARP/MILS m.8993T > G mutation was present in this series [ 58 ]. In our own experience RP is invariant in this mutation, which is relatively frequent in mitochondrial disease patients.…”

Section: Genetic Heterogeneity In Mitochondrial Rpmentioning

confidence: 99%

Mitochondrial Retinopathies

Zeviani

Carelli

2021

IJMS

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The retina is an exquisite target for defects of oxidative phosphorylation (OXPHOS) associated with mitochondrial impairment. Retinal involvement occurs in two ways, retinal dystrophy (retinitis pigmentosa) and subacute or chronic optic atrophy, which are the most common clinical entities. Both can present as isolated or virtually exclusive conditions, or as part of more complex, frequently multisystem syndromes. In most cases, mutations of mtDNA have been found in association with mitochondrial retinopathy. The main genetic abnormalities of mtDNA include mutations associated with neurogenic muscle weakness, ataxia and retinitis pigmentosa (NARP) sometimes with earlier onset and increased severity (maternally inherited Leigh syndrome, MILS), single large-scale deletions determining Kearns–Sayre syndrome (KSS, of which retinal dystrophy is a cardinal symptom), and mutations, particularly in mtDNA-encoded ND genes, associated with Leber hereditary optic neuropathy (LHON). However, mutations in nuclear genes can also cause mitochondrial retinopathy, including autosomal recessive phenocopies of LHON, and slowly progressive optic atrophy caused by dominant or, more rarely, recessive, mutations in the fusion/mitochondrial shaping protein OPA1, encoded by a nuclear gene on chromosome 3q29.

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“…The retinal phenotype also may be the first indication of a mitochondrial disease. Specific retinal changes may be a characteristic finding in a variety of mitochondrial diseases and have been reported in a PEO with RRM2B mutation, indicating that it is crucial for achieving the systemic diagnosis (Birtel et al, 2021 ). Therefore, the further clinical follow‐up for these patients is important.…”

Section: Discussionmentioning

confidence: 99%

Novel and recurrent nuclear gene variations in a cohort of Chinese progressive external ophthalmoplegia patients with multiple mtDNA deletions

Hou

Zhao

Xie

et al. 2022

Molec Gen & Gen Med

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Objectives This study aimed to investigate the clinical and genetic spectrum in Chinese patients with multiple mtDNA deletions presenting with autosomal‐inherited mitochondrial progressive external ophthalmoplegia (PEO). Methods Long‐range polymerase chain reaction and massively parallel sequencing of the mitochondrial genome were performed to detect deletions in muscle mtDNA of 274 unrelated families. Then, targeted next generation sequencing was used to detect nuclear gene variations in patients with multiple mtDNA deletions. Results A total of 40 Chinese PEO patients (10 males and 30 females) from 20 families were found to have multiple mtDNA deletions in this study, and the median age at onset was 35 (1–70) years. PEO and positive family history were the two prominent features of these patients, and ataxia, neuropathy, and hypogonadism were also present as onset symptoms in some patients. Fifteen of 20 probands with multiple mtDNA deletions were identified to carry nuclear gene variants; eight (40.0%) probands had variants within POLG , two (10.0%) within TWNK , two (10.0%) within RRM2B , two (10.0%) within TK2 , and one (5.0%) within POLG2 . A total of 24 variants were found in these five nuclear genes, of which 19 were novel. The causal nuclear genetic factors in five pedigrees remain undetermined. Conclusions The POLG gene is the most common disease‐causing gene in this group of PEO patients with multiple mtDNA deletions. While inherited PEO is the most prominent symptoms in these patients, genotypic and phenotypic heterogeneity still exist, for example in onset age, initial symptoms, and accompanying manifestations.

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Mitochondrial Retinopathy

Cited by 37 publications

References 53 publications

Visible Light Optical Coherence Tomography Reveals the Relationship of the Myoid and Ellipsoid to Band 2 in Humans

Visible Light Optical Coherence Tomography Reveals the Relationship of the Myoid and Ellipsoid to Band 2 in Humans

Mitochondrial Retinopathies

Novel and recurrent nuclear gene variations in a cohort of Chinese progressive external ophthalmoplegia patients with multiple mtDNA deletions

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