Mitochondrial Dysfunction in Retinal Diseases

Barot, Megha; Gokulgandhi, Mitan; Mitra, Ashim K.

doi:10.3109/02713683.2011.607536

Cited by 151 publications

(133 citation statements)

References 77 publications

(86 reference statements)

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“…Experimental findings have also shown a link between mitochondrial impairment and RPE degeneration, which would arise as a consequence of an in-balance of the cellular redox system. In particular, mitochondrial depolarization has been reported to precede RPE cell death caused by peroxidation by the reduction of energy production, the increased Cytochrome c release and ROS generation [36-38]. …”

Section: Discussionmentioning

confidence: 99%

Anti-Vascular Endothelial Growth Factors Protect Retinal Pigment Epithelium Cells Against Oxidation by Modulating Nitric Oxide Release and Autophagy

Cillà

Farruggio

Vujosevic

et al. 2017

Cell Physiol Biochem

3,602

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Background/Aims: the anti-vascular endothelial growth factors (VEGF), Aflibercept and Ranibizumab, are used for the treatment of macular degeneration. Here we examined the involvement of nitric oxide (NO), mitochondria function and of apoptosis/autophagy in their antioxidant effects in human retinal pigment epithelium cells (RPE). Methods: RPE were exposed to Ranibizumab/Aflibercept in the absence or presence of NO synthase (NOS) inhibitor and of autophagy activator/blocker, rapamicyn/3-methyladenine. Specific kits were used for cell viability, NO and reactive oxygen species detection and mitochondrial membrane potential measurement, whereas Western Blot was performed for apoptosis/ autophagy markers and other kinases detection. Results: In RPE cultured in physiological conditions, Aflibercept/Ranibizumab increased NO release in a dose and time-dependent way. Opposite results were obtained in RPE pretreated with hydrogen peroxide. Moreover, both the anti-VEGF agents were able to prevent the fall of cell viability and of mitochondrial membrane potential. Those effects were reduced by the NOS inhibitor and 3-methyladenine and were potentiated by rapamycin. Finally, Aflibercept and Ranibizumab counteracted the changes of apoptosis/autophagy markers, NOS, Phosphatidylinositol-3-Kinase/Protein Kinase B and Extracellular signal–regulated kinases 1/2 caused by peroxidation. Conclusion: Aflibercept and Ranibizumab protect RPE against peroxidation through the modulation of NO release, apoptosis and autophagy.

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Section: Discussionmentioning

confidence: 99%

Anti-Vascular Endothelial Growth Factors Protect Retinal Pigment Epithelium Cells Against Oxidation by Modulating Nitric Oxide Release and Autophagy

Cillà

Farruggio

Vujosevic

et al. 2017

Cell Physiol Biochem

3,602

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“…21 There is a growing body of evidence in support of an association of mitochondrial dysfunction with retinal degenerative diseases including AMD. 35 It is thought that the accelerated senescence and development of age-related diseases in OXYS rats is also linked with progressive mitochondrial dysfunction. 21,23,36 Thus, we can hypothesize that SkQ1 protects against stress and restores mitochondrial function in the retina of OXYS rats.…”

Section: Discussionmentioning

confidence: 99%

The mitochondria-targeted antioxidant SkQ1 restoresαB-crystallin expression and protects against AMD-like retinopathy in OXYS rats

et al. 2014

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Abbreviations: AMD, age-related macular degeneration; RPE, retinal pigment epithelium; SkQ1, 10-(6 0 plastoquinonyl)decyltriphenylphosphonium.Age-related macular degeneration (AMD), a neurodegenerative and vascular retinal disease, is the leading cause of blindness in the developed world. Accumulating evidence suggests that alterations in the expression of a small heat shock protein (aB-crystallin) are involved in the pathogeneses of AMD. Here we demonstrate that senescenceaccelerated OXYS rats-an animal model of the dry form of AMD-develop spontaneous retinopathy against the background of reduced expression of aB-crystallin in the retina at the early preclinical stages of retinopathy (age 20 days) as well as at 4 and 24 months of age, during the progressive stage of the disease. The level of aA-crystallin expression in the retina of OXYS rats at all the ages examined was no different from that in disease-free Wistar rats. Treatment with the mitochondria-targeted antioxidant SkQ1 (plastoquinonyl-decyltriphenylphosphonium) from 1.5 to 4 months of age, 250 nmol/kg, increased the level of aB-crystallin expression in the retina of OXYS rats. SkQ1 slowed the development of retinopathy and reduced histological aberrations in retinal pigment epithelium cells. SkQ1 also attenuated neurodegenerative changes in the photoreceptors and facilitated circulation in choroid blood vessels in the retina of OXYS rats; this improvement was probably linked with the restoration of aB-crystallin expression.

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“…Approximately 50% of mitochondrial disorders have an ocular phenotype [9]. In addition to dominant optic atrophy (DOA) [10] and LHON (Box 1 [11]), mitochondrial dysfunction has been linked to multifactorial diseases, including age-related macular degeneration (AMD) [7,12] and diabetic retinopathies [12], as well as complex disorders involving multiple tissues, including the eye, such as neuropathy, ataxia and retinitis pigmentosa (NARP) and Kearns-Sayre syndrome (KSS) [13,14].…”

Section: Mitochondrial Dysfunction In Human Disordersmentioning

confidence: 99%