670nm light treatment following retinal injury modulates Müller cell gliosis: Evidence from in vivo and in vitro stress models

Lu, Yang; Fernando, Nilisha; Natoli, Riccardo; Madigan, Michele C.; Valter, Krisztina

doi:10.1016/j.exer.2018.01.011

Cited by 16 publications

(25 citation statements)

References 55 publications

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“…Histological analyses revealed a moderate degree of stress in photoreceptors localized in the site of "implant, " in the absence of adverse effects on the retinal structure outside the implant area. In the retina, GFAP is constitutively expressed in astrocytes and Muller cells, and becomes upregulated under stress conditions (Lewis and Fisher, 2003;Edwards et al, 2016;Luna et al, 2016;Zhang et al, 2017;Lu et al, 2018). Interestingly, we observed no changes in GFAP expression after 10 days of surgery in both sham-implanted and prosthesis-implanted eyes as compared to non-implanted controls.…”

Section: Discussionmentioning

confidence: 50%

“…Glial fibrillary acidic protein expression correlates with neuroinflammation (Brahmachari et al, 2006;Kim et al, 2016;Zhang et al, 2017). In the retina, GFAP is constitutively expressed in astrocytes and Muller cell's soma; it is upregulated following stress and, in Muller cells, translocated along their outer and inner branches (Lewis and Fisher, 2003;Edwards et al, 2016;Luna et al, 2016;Zhang et al, 2017;Lu et al, 2018) (Figure 8A). No significant changes in GFAP levels were found between shamor prosthesis-implanted and control animals ( Figure 8B).…”

Section: Biocompatibility Of the Pet-based Implantmentioning

confidence: 99%

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Biocompatibility of a Conjugated Polymer Retinal Prosthesis in the Domestic Pig

Maya‐Vetencourt

Marco

Mete

et al. 2020

Front. Bioeng. Biotechnol.

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The progressive degeneration of retinal photoreceptors is one of the most significant causes of blindness in humans. Conjugated polymers represent an attractive solution to the field of retinal prostheses, and a multi-layer fully organic prosthesis implanted subretinally in dystrophic Royal College of Surgeons (RCS) rats was able to rescue visual functions. As a step toward human translation, we report here the fabrication and in vivo testing of a similar device engineered to adapt to the human-like size of the eye of the domestic pig, an excellent animal paradigm to test therapeutic strategies for photoreceptors degeneration. The active conjugated polymers were layered onto two distinct passive substrates, namely electro-spun silk fibroin (ESF) and polyethylene terephthalate (PET). Naive pigs were implanted subretinally with the active device in one eye, while the contralateral eye was sham implanted with substrate only. Retinal morphology and functionality were assessed before and after surgery by means of in vivo optical coherence tomography and full-field electroretinogram (ff-ERG) analysis. After the sacrifice, the retina morphology and inflammatory markers were analyzed by immunohistochemistry of the excised retinas. Surprisingly, ESF-based prostheses caused a proliferative vitreoretinopathy with disappearance of the ff-ERG b-wave in the implanted eyes. In contrast, PET-based active devices did not evoke significant inflammatory responses. As expected, the subretinal implantation of both PET only and the PET-based prosthesis locally decreased the thickness of the outer nuclear layer due to local photoreceptor loss. However, while the implantation of the PET only substrate decreased the ff-ERG b-wave amplitude with respect to the pre-implant ERG, the eyes implanted with the active device fully preserved the ERG responses, indicating an active compensation of the surgery-induced photoreceptor loss. Our findings highlight the possibility of developing a new generation of conjugated polymer/PET-based prosthetic devices that are highly biocompatible and potentially suitable for subretinal implantation in patients suffering from degenerative blindness.

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Section: Discussionmentioning

confidence: 50%

Section: Biocompatibility Of the Pet-based Implantmentioning

confidence: 99%

Biocompatibility of a Conjugated Polymer Retinal Prosthesis in the Domestic Pig

Maya‐Vetencourt

Marco

Mete

et al. 2020

Front. Bioeng. Biotechnol.

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“…Cells were validated for species authenticity (CellBank, Sydney, AUS). These cells were cultured as previously published 85 , in growth medium containing Dulbecco's Modified Eagle Medium (DMEM; Sigma-Aldrich) supplemented with 10% fetal bovine serum (FBS; Sigma-Aldrich, MO, USA), 6 mM L-glutamine (Thermo Fisher Scientific, MA, USA) and antibiotic-antimycotic (100U/ml penicillin, 100 μg/ml streptomycin; Thermo Fisher Scientific, MA, USA). Cells were maintained in dim conditions in a humidified atmosphere of 5% CO 2 at 37 °C, and passaged by trypsinization every 3-4 days.…”

Section: Optical Coherence Tomography (Oct)mentioning

confidence: 99%

“…Immunohistochemical analysis of retinal cryosections was performed as previously described 62 . Immunocytochemistry was performed using a protocol previously described 85 . Haematoxylin and Eosin staining was performed by covering the retinal cryosections in 1x PBS for 10 minutes, followed by 3 minutes in 95% ethanol and 3 minutes in 70% ethanol.…”

Section: Optical Coherence Tomography (Oct)mentioning

confidence: 99%

Caspase-1-dependent inflammasomes mediate photoreceptor cell death in photo-oxidative damage-induced retinal degeneration

Wooff

Fernando

Wong

et al. 2020

Sci Rep

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Activation of the inflammasome is involved in the progression of retinal degenerative diseases, in particular, in the pathogenesis of Age-Related Macular Degeneration (AMD), with NLRP3 activation the focus of many investigations. In this study, we used genetic and pharmacological approaches to explore the role of the inflammasome in a mouse model of retinal degeneration. We identify that Casp1/11 −/− mice have better-preserved retinal function, reduced inflammation and increased photoreceptor survivability. While Nlrp3 −/− mice display some level of preservation of retinal function compared to controls, pharmacological inhibition of NLRP3 did not protect against photoreceptor cell death. Further, Aim2 −/− , Nlrc4 −/− , Asc −/− , and Casp11 −/− mice show no substantial retinal protection. We propose that CASP-1-associated photoreceptor cell death occurs largely independently of NLRP3 and other established inflammasome sensor proteins, or that inhibition of a single sensor is not sufficient to repress the inflammatory cascade. Therapeutic targeting of CASP-1 may offer a more promising avenue to delay the progression of retinal degenerations. Age-Related Macular Degeneration (AMD) is a chronic inflammatory disease that is characterised by central vision loss due to retinal pigmented epithelium (RPE) and photoreceptor cell death in the macular region of the retina 1,2. While environmental, lifestyle and genetic risk factors are well established 2-4 , it is increasingly clear that central to disease progression is the accumulation of oxidative stress 5 and inflammation 6. A central component of inflammation is the inflammasome, multi-protein oligomers which form part of the innate immune system, acting in the first line of defence, sensing pathogen-derived or danger signals from pathogen invasion, or cellular stress signals including extracellular ATP or host dsDNA 1,7-9. Inflammasomes are composed of a pattern recognition receptor (PRR) sensor protein, including NACHT, LRR and PYD domains-containing protein 1 (NLRP1), NLRP3, NAIP-NLRC4, Absent in Melanoma 2 (AIM2), and Pyrin. Following activation, these sensor proteins form a complex with the adaptor protein Apoptosis-associated speck-like protein containing a CARD (ASC, or PYCARD) and protease enzyme Caspase-1 (CASP-1) 10,11. Activated CASP-1 in turn, cleaves and activates pro-inflammatory cytokines including interleukin-1β (IL-1β), large amounts of which are known to cause microglial activation and macrophage recruitment from the periphery, and ultimately photoreceptor cell death, characteristic features of AMD pathogenesis 3,8,12-16. Inhibition of IL-1β has been shown to reduce inflammation and further cell death 14 , highlighting the key role of the inflammasome in the progression of retinal degenerative diseases such as AMD.

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“…In recent years, there has been an increasing interest in using PBM for therapy of retinal diseases. Protective functions were reported for different neuronal and nonneuronal retinal cell types, i.e., photoreceptors, the retinal pigment epithelium (RPE), retinal ganglion cells and Müller cells [4,[13][14][15][16][17][18][19][20]. Besides studying individual cell types, several studies focus on effects in different diseases models such as age-related macular degeneration (AMD) and retinopathy models for possible transfer into therapy [18,[21][22][23][24][25][26].…”

Section: Introductionmentioning

confidence: 99%

Photobiomodulation Mediates Neuroprotection against Blue Light Induced Retinal Photoreceptor Degeneration

Heinig

Schumann

Calzia

et al. 2020

IJMS

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Potent neuroprotective effects of photobiomodulation with 670 nm red light (RL) have been demonstrated in several models of retinal disease. RL improves mitochondrial metabolism, reduces retinal inflammation and oxidative cell stress, showing its ability to enhance visual function. However, the current knowledge is limited to the main hypothesis that the respiratory chain complex IV, cytochrome c oxidase, serves as the primary target of RL. Here, we demonstrate a comprehensive cellular, molecular, and functional characterization of neuroprotective effects of 670 nm RL and 810 nm near-infrared light (NIRL) on blue light damaged murine primary photoreceptors. We show that respiratory chain complexes I and II are additional PBM targets, besides complex IV, leading to enhanced mitochondrial energy metabolism. Accordingly, our study identified mitochondria related RL- and NIRL-triggered defense mechanisms promoting photoreceptor neuroprotection. The observed improvement of mitochondrial and extramitochondrial respiration in both inner and outer segments is linked with reduced oxidative stress including its cellular consequences and reduced mitochondria-induced apoptosis. Analysis of regulatory mechanisms using gene expression analysis identified upregulation α-crystallins that indicate enhanced production of proteins with protective functions that point to the rescued mitochondrial function. The results support the hypothesis that energy metabolism is a major target for retinal light therapy.

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670nm light treatment following retinal injury modulates Müller cell gliosis: Evidence from in vivo and in vitro stress models

Cited by 16 publications

References 55 publications

Biocompatibility of a Conjugated Polymer Retinal Prosthesis in the Domestic Pig

Biocompatibility of a Conjugated Polymer Retinal Prosthesis in the Domestic Pig

Caspase-1-dependent inflammasomes mediate photoreceptor cell death in photo-oxidative damage-induced retinal degeneration

Photobiomodulation Mediates Neuroprotection against Blue Light Induced Retinal Photoreceptor Degeneration

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