Pharmacological approaches to retinitis pigmentosa: A laboratory perspective

Guadagni, Viviana; Novelli, Elena; Piano, Ilaria; Gargini, Claudia; Strettoi, Enrica

doi:10.1016/j.preteyeres.2015.06.005

Cited by 82 publications

(67 citation statements)

References 171 publications

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“…Treatment options for RP, other than 137 for the associated cataract, epiretinal membrane and macular oedema, are 138 limited (Guadagni et al, 2015). As such, they represent an ideal group of 139 patients who may benefit from retinal prosthesis treatment.…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

The Argus® II Retinal Prosthesis System

Luo

Cruz

2016

Progress in Retinal and Eye Research

307

270

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Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

The Argus® II Retinal Prosthesis System

Luo

Cruz

2016

Progress in Retinal and Eye Research

307

270

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“…Vitamin A, docosahexaenoic acid and valproic acid were found to slow the visual function loss and show positive effects in RP patients 4–6 . Other pharmacological treatments including neurotrophic factors and anti-inflammatory factors are still on their way to being used to treat patients 7–9 . Potential cell transplantation is now becoming a promising way to rescue dead cells and reform neural connections in animal models 10–14 .…”

Section: Introductionmentioning

confidence: 99%

Combined transplantation of human mesenchymal stem cells and human retinal progenitor cells into the subretinal space of RCS rats

Gao

et al. 2017

Sci Rep

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Retinitis pigmentosa (RP) is one of hereditary retinal diseases characterized by the loss of photoreceptors. Cell transplantation has been clinically applied to treat RP patients. Human retinal progenitor cells (HRPCs) and human bone marrow-derived mesenchymal stem cells (HBMSCs) are the two commonly and practically used stem cells for transplantation. Since combined transplantation could be a promising way to integrate the advantages of both stem cell types, we transplanted HRPCs and HBMSCs into the subretinal space (SRS) of Royal College of Surgeons (RCS) rats. We report that HRPCs/HBMSCs combined transplantation maintains the electroretinogram results much better than HRPCs or HBMSCs single transplantations. The thickness of outer nuclear layer also presented a better outcome in the combined transplantation. Importantly, grafted cells in the combination migrated better, both longitudinally and latitudinally, than single transplantation. The photoreceptor differentiation of grafted cells in the retina of RCS rats receiving combined transplantation also showed a higher ratio than single transplantation. Finally, activation of microglia and the gliosis of Müller cells were more effectively suppressed in combined transplantation, indicating better immunomodulatory and anti-gliosis effects. Taken together, combining the transplantation of HRPCs and HBMSCs is a more effective strategy in stem cell-based therapy for retinal degenerative diseases.

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“…For example, although the presence of inflammatory markers has been recognized in rodent models of RP for a long time, the occurrence of immune system cells in the anterior vitreous cavity of RP subjects has only recently been reported by slit-lamp biomicroscopy [8]. The use of Iba1 specific antibodies by others and us has also revealed that microglial cells, which normally reside in the outer plexiform layer, become activated from the very beginning of photoreceptor death in T17M [4], Rd10 [18], and MERTK −/− [19] mice. The up-regulation of pro-inflammatory mRNAs in Rd and T17M mice also occurs prior to peak photoreceptor cell death [4,20].…”

Section: Introductionmentioning

confidence: 99%

TNFa knockdown in the retina promotes cone survival in a mouse model of autosomal dominant retinitis pigmentosa

Rana

Kotla

Fullard

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Expression of T17M rhodopsin (T17M) in rods activates the Unfolded Protein Response (UPR) and leads to the development of autosomal dominant retinitis pigmentosa (adRP). The rod death occurs in adRP retinas prior to cone photoreceptor death, so the mechanism by which cone photoreceptors die remains unclear. Therefore, the goal of the study was to verify whether UPR in rods induces TNFa-mediated signaling to the cones and to determine whether the TNFa deficit could prevent adRP cone cell death. Primary rod photoreceptors and cone-derived 661Wcells transfected with siRNA against TNFa were treated with tunicamycin to mimic activation of UPR in T17M retinas expressing normal and reduced TNFa levels. The 661W cells were then exposed to recombinant TNFa to evaluate cell viability. In vivo, the role of TNFa was assessed in T17M TNFa+/− mice by electroretinography, optical coherence tomography, histology, immunohistochemistry, and a cytokine enzyme-linked immunosorbent assay. Rods overexpressed and secreted TNFa in response to UPR activation. The recombinant TNFa treatment lowered the number of viable cones, inducing cell death through elevation of pro-inflammatory cytokines and caspase-3/7 activity. The TNFa deficiency significantly protected adRP retinas. The photopic ERG amplitudes and the number of surviving cones dramatically increased in T17M TNFa+/− mice. This neuroprotection was associated with a reduced level of pro-inflammatory cytokines. Our results indicate that rod photoreceptors, following UPR activation during adRP progression, secrete TNFa and signal a self-destructive program to the cones, resulting in their cell death. TNFa therefore holds promise as a therapeutic target for treatment of adRP.

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Pharmacological approaches to retinitis pigmentosa: A laboratory perspective

Cited by 82 publications

References 171 publications

The Argus® II Retinal Prosthesis System

The Argus® II Retinal Prosthesis System

Combined transplantation of human mesenchymal stem cells and human retinal progenitor cells into the subretinal space of RCS rats

TNFa knockdown in the retina promotes cone survival in a mouse model of autosomal dominant retinitis pigmentosa

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