Long-term evaluation of Leber’s hereditary optic neuropathy-like symptoms in rotenone administered rats

Zhang, Li; Philip, Ann; Martı́nez, Juan Carlos; Guttierez, Juan C.; Marella, Mathieu; Patki, Gaurav; Matsuno‐Yagi, Akemi; Yagi, Takao; Thomas, Biju

doi:10.1016/j.neulet.2014.12.004

Cited by 10 publications

(5 citation statements)

References 29 publications

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“…As such, this was the first paper to report that significant alterations in the retina occur before the classical PD symptoms in the brain and to claim that the retina can be used as a potential biomarker tissue for early diagnosis [93]. Inner retinal layer thinning was also confirmed in other studies using the rodent rotenone model, in addition to decreased expression of dopaminergic cell markers and photoreceptor loss [42,119,155,157]. While little attention has been devoted to retinal αSYN deposits, retinal function and structure have been studied more intensively in toxin-induced models, and has unveiled the importance of dopaminergic signalling in the retina.…”

Section: Toxin-induced Modelsmentioning

confidence: 60%

Retinal α-synuclein deposits in Parkinson’s disease patients and animal models

et al. 2019

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Despite decades of research, accurate diagnosis of Parkinson's disease remains a challenge, and disease-modifying treatments are still lacking. Research into the early (presymptomatic) stages of Parkinson's disease and the discovery of novel biomarkers is of utmost importance to reduce this burden and to come to a more accurate diagnosis at the very onset of the disease. Many have speculated that non-motor symptoms could provide a breakthrough in the quest for early biomarkers of Parkinson's disease, including the visual disturbances and retinal abnormalities that are seen in the majority of Parkinson's disease patients. An expanding number of clinical studies have investigated the use of in vivo assessments of retinal structure, electrophysiological function, and vision-driven tasks as novel means for identifying patients at risk that need further neurological examination and for longitudinal follow-up of disease progression in Parkinson's disease patients. Often, the results of these studies have been interpreted in relation to α-synuclein deposits and dopamine deficiency in the retina, mirroring the defining pathological features of Parkinson's disease in the brain. To better understand the visual defects seen in Parkinson's disease patients and to propel the use of retinal changes as biomarkers for Parkinson's disease, however, more conclusive neuropathological evidence for the presence of retinal α-synuclein aggregates, and its relation to the cerebral α-synuclein burden, is urgently needed. This review provides a comprehensive and critical overview of the research conducted to unveil α-synuclein aggregates in the retina of Parkinson's disease patients and animal models, and thereby aims to aid the ongoing discussion about the potential use of the retinal changes and/or visual symptoms as biomarkers for Parkinson's disease.

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Section: Toxin-induced Modelsmentioning

confidence: 60%

Retinal α-synuclein deposits in Parkinson’s disease patients and animal models

et al. 2019

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“…In conclusion, we investigated the potential roles of glial cells and their secretion in rotenone-induced retinal degeneration re ecting the pathology of mitochondrial oxidative stress-induced retinal diseases 13,16,17 . Since microglia-derived NTF5 may promote retinal cell survival, NTF5 administration might be effective for treating oxidative stress-associated retinal degeneration diseases.…”

Section: Discussionmentioning

confidence: 99%

Glial Cells Modulate Retinal Cell Survival in Rotenone-Induced Neural Degeneration

Tawarayama

Inoue-Yanagimachi

Himori

et al. 2021

Preprint

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Administration of the mitochondrial complex I inhibitor rotenone provides an excellent model to study the pathomechanism of oxidative stress-related neural degeneration diseases. In this study, we examined the glial roles in retinal cell survival and degeneration under the rotenone-induced oxidative stress condition. Mouse-derived Müller, microglial (BV-2), and dissociated retinal cells were used for in vitro experiments. Gene expression levels and cell viability were determined using quantitative reverse transcription-polymerase chain reaction and the alamarBlue assay, respectively. Conditioned media were prepared by stimulating glial cells with rotenone. Retinal ganglion cells (RGCs) and inner nuclear layer (INL) were visualized on rat retinal sections by immunohistochemistry and eosin/hematoxylin, respectively. Rotenone dose-dependently induced glial cell death. Treatment with rotenone or rotenone-stimulated glial cell-conditioned media altered gene expression of growth factors and inflammatory cytokines in glial cells. The viability of dissociated retinal cells significantly increased upon culturing in media conditioned with rotenone-stimulated or Müller cell-conditioned media-stimulated BV-2 cells. Furthermore, intravitreal neurotrophin-5 administration prevented the rotenone-induced reduction of RGC number and INL thickness in rats. Thus, glial cells exerted both positive and negative effects on retinal cell survival in rotenone-induced neural degeneration via altered expression of growth factors, especially upregulation of microglia-derived Ntf5, and proinflammatory cytokines.

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“…Rotenone is a CI inhibitor that has been used to generate animal models of LHON [39]. Thus, following a daily intraperitoneal rotenone administration for 10 days, an increase in RGC apoptosis was observed.…”

Section: Protective Effects Of Retinal Ganglion Cellsmentioning

confidence: 99%

Increasing mtDNA levels as therapy for mitochondrial optic neuropathies

Ruiz‐Pesini

Emperador

López‐Gallardo

et al. 2018

Drug Discovery Today

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Leber hereditary optic neuropathy (LHON) is a rare, inherited mitochondrial disease. No treatment has shown a clear-cut benefit on a clinically meaningful end-point. Primary open-angle glaucoma (POAG) is a frequent, acquired optic neuropathy. Lowering intraocular pressure (IOP) reduces disease progression. However, current methods to decelerate this progression are recognized as being inadequate. Therefore, there is a clear need to look for new therapeutic approaches. The growing evidence indicates that POAG can also be a mitochondrial optic neuropathy (MON). Several risk elements are common for both diseases and all of them decrease mitochondrial (mt)DNA content. Based on these susceptibility factors and their molecular mechanism, we suggest herein pharmacological therapies targeted to increase mtDNA levels, oxidative phosphorylation (OXPHOS) capability, and mitochondrial energy production as treatments for MONs.

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Long-term evaluation of Leber’s hereditary optic neuropathy-like symptoms in rotenone administered rats

Cited by 10 publications

References 29 publications

Retinal α-synuclein deposits in Parkinson’s disease patients and animal models

Retinal α-synuclein deposits in Parkinson’s disease patients and animal models

Glial Cells Modulate Retinal Cell Survival in Rotenone-Induced Neural Degeneration

Increasing mtDNA levels as therapy for mitochondrial optic neuropathies

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