Stress Reaction in Outer Segments of Photoreceptors after Blue Light Irradiation

Roehlecke, Cora; Schumann, Ulrike; Ader, Marius; Brunßen, Coy; Bramke, Silvia; Morawietz, Henning; Funk, Richard

doi:10.1371/journal.pone.0071570

Cited by 91 publications

(94 citation statements)

References 37 publications

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“…In the light-induced model of photoreceptor degeneration in mouse, superoxide radicals and other ROS contribute to photoreceptor apoptosis 25 and RAC1 has been linked to photoreceptor cell loss. 40,63 A recent study 64 has found that NOX mediates ROS generation and oxidative damage in mouse photoreceptors after blue light damage. In addition, RAC1-NOX–dependent superoxide generation is responsible for light-induced degeneration of Crumbs-deficient photoreceptor cells in Drosophila .…”

Section: Discussionmentioning

confidence: 99%

NADPH Oxidase Contributes to Photoreceptor Degeneration in Constitutively Active RAC1 Mice

Song

Vijayasarathy

Zeng

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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PurposeThe active form of small GTPase RAC1 is required for activation of NADPH oxidase (NOX), which in turn generates reactive oxygen species (ROS) in nonphagocytic cells. We explored whether NOX-induced oxidative stress contributes to rod degeneration in retinas expressing constitutively active (CA) RAC1.MethodsTransgenic (Tg)–CA-RAC1 mice were given apocynin (10 mg/kg, intraperitoneal), a NOX inhibitor, or vehicle daily for up to 13 weeks. Superoxide production and oxidative damage were assessed by dihydroethidium staining and by protein carbonyls and malondialdehyde levels, respectively. Outer nuclear layer (ONL) cells were counted and electroretinogram (ERG) amplitudes measured in Tg-CA-RAC1 mice. Outer nuclear layer cells were counted in wild-type (WT) mice after transfer of CA-Rac1 gene by subretinal injection of AAV8-pOpsin-CA Rac1-GFP.ResultsTransgenic-CA-RAC1 retinas had significantly fewer photoreceptor cells and more apoptotic ONL cells than WT controls from postnatal week (Pw) 3 to Pw13. Superoxide accumulation and protein and lipid oxidation were increased in Tg-CA-RAC1 retinas and were reduced in mice treated with apocynin. Apocynin reduced the loss of photoreceptors and increased the rod ERG a- and b-wave amplitudes when compared with vehicle-injected transgenic controls. Photoreceptor loss was also observed in regions of adult WT retina transduced with AAV8-pOpsin-CA Rac1-GFP but not in neighboring regions that were not transduced or in AAV8-pOpsin-GFP–transduced retinas.ConclusionsConstitutively active RAC1 promotes photoreceptor cell death by oxidative damage that occurs, at least partially, through NOX-induced ROS. Reactive oxygen species are likely involved in multiple forms of retinal degenerations, and our results support investigating RAC1 inhibition as a therapeutic approach that targets this disease pathway.

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Section: Discussionmentioning

confidence: 99%

NADPH Oxidase Contributes to Photoreceptor Degeneration in Constitutively Active RAC1 Mice

Song

Vijayasarathy

Zeng

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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“…Mitochondrial membrane potential. Mitochondrial membrane potential (MMP) was assessed by measuring the potential-dependent accumulation of 5,5=,6,6=-tetrachloro-1,1=,3,3=-tetraethylbenzimdazol carbocyanine iodide (JC-1; Molecular Probes) or tetramethylrhodamine ethyl ester (Invitrogen-Molecular Probes) (27). As previously described (1), the isolated mitochondrial pellet and dissociated podocytes were washed twice with HBSS (Sigma) and then incubated in the dark with JC-1 (7.5 M) for 30 min at 37°C.…”

Section: Methodsmentioning

confidence: 99%

Dysfunction of the PGC-1α-mitochondria axis confers adriamycin-induced podocyte injury

Zhu

Xuan

Che

et al. 2014

American Journal of Physiology-Renal Physiology

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Adriamycin (ADR)-induced nephropathy in animals is an experimental analog of human focal segmental glomerulosclerosis, which presents as severe podocyte injury and massive proteinuria and has a poorly understood mechanism. The present study was designed to test the hypothesis that the peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α-mitochondria axis is involved in ADR-induced podocyte injury. Using MPC5 immortalized mouse podocytes, ADR dose dependently induced downregulation of nephrin and podocin, cell apoptosis, and mitochondrial dysfunction based on the increase in mitochondrial ROS production, decrease in mitochondrial DNA copy number, and reduction of mitochondrial membrane potential and ATP content. Moreover, ADR treatment also remarkably reduced the expression of PGC-1α, an important regulator of mitochondrial biogenesis and function, in podocytes. Strikingly, PGC-1α overexpression markedly attenuated mitochondrial dysfunction, the reduction of nephrin and podocin, and the apoptotic response in podocytes after ADR treatment. Moreover, downregulation of PGC-1α and mitochondria disruption in podocytes were also observed in rat kidneys with ADR administration, suggesting that the PGC-1α-mitochondria axis is relevant to in vivo ADR-induced podocyte damage. Taken together, these novel findings suggest that dysfunction of the PGC-1α-mitochondria axis is highly involved in ADR-induced podocyte injury. Targeting PGC-1α may be a novel strategy for the treatment of ADR nephropathy and human focal segmental glomerulosclerosis.

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“…It was performed to see the level of expression of GFAP, AQP1 and AQP4 in the retina among the three experimental groups (N = 24, 8 retina/group, Table 1 [40,41]. The specificity of the antibodies was also confirmed by performing Western blot of proteins extracted from rat retina.…”

Section: Western Immunoblottingmentioning

confidence: 99%

Differential Expression of AQP1 and AQP4 in Avascular Chick Retina Exposed to Moderate Light of Variable Photoperiods

et al. 2015

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Aquaporins (AQPs) are integral membrane proteins which maintain cellular water and ion homeostasis. Alterations in AQP expression have been reported in rod-dominated rodent retinas exposed to light. In rodents and also in birds, light of moderate intensities (700-2000 lux) damages the retina, though detailed changes were not examined in birds. The aim of our study was to see if light affects cone dominated retinas, which would be reflected in expression levels of AQPs. We examined AQP1 and AQP4 expressions in chick retina exposed to 2000 lux under 12 h light:12 h dark (12L:12D; normal photoperiod), 18L:6D (prolonged photoperiod) and 24L:0D (constant light). Additionally, morphological changes, apoptosis (by TUNEL) and levels of glutamate and GFAP (a marker of injury) in the retina were examined to correlate these with AQP expressions. Constant light caused damage in outer and inner nuclear layer (ONL, INL) and ganglion cell layer (GCL). Also, there were associated increases in GFAP and glutamate levels in retinal extracts. In normal photoperiod, AQP1 was expressed in GCL, outer part of INL and photoreceptor inner segments of. AQP4 was additionally expressed in nerve fiber layer. Immunohistochemistry and Western blotting revealed over all decreased AQP1 and AQP4 expression in constant light condition compared to those in other two groups. The elevated GFAP and glutamate levels might be involved in the reduction of AQPs in constant light group. Such decreases in AQP expressions are perhaps linked with retinal cell damage seen in constant light condition, while their relatively enhanced expression in two other conditions may help in maintaining a normal retinal architecture, indicating their neuroprotective potential.

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Stress Reaction in Outer Segments of Photoreceptors after Blue Light Irradiation

Cited by 91 publications

References 37 publications

NADPH Oxidase Contributes to Photoreceptor Degeneration in Constitutively Active RAC1 Mice

NADPH Oxidase Contributes to Photoreceptor Degeneration in Constitutively Active RAC1 Mice

Dysfunction of the PGC-1α-mitochondria axis confers adriamycin-induced podocyte injury

Differential Expression of AQP1 and AQP4 in Avascular Chick Retina Exposed to Moderate Light of Variable Photoperiods

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