Long time remodeling during retinal degeneration evaluated by optical coherence tomography, immunocytochemistry and fundus autofluorescence

Pinilla, Isabel; Fernández‐Sánchez, Laura; Segura, Francisco; Sánchez‐Cano, Ana; Tamarit, José Manuel; Fuentes-Broto, Lorena; Eells, Janis T.; Lax, Pedro; Cuenca, Nicolás

doi:10.1016/j.exer.2015.10.012

Cited by 28 publications

(39 citation statements)

References 74 publications

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“…Scaling of the OCT data with histology at this scale is not very informative other than as a demonstration of what current clinical imaging can resolve in end stage RP. While it is not possible to identify any normal cells or layering once the normal lamination of the retina is lost in end-stage RP, OCT results in earlier stages of retinal degeneration are more feasible as shown by (Pinilla et al, 2015) with the P23H rat. Müller cells and large zones of unknown cells now dominate the remnant retina.…”

Section: 0 Resultsmentioning

confidence: 99%

Retinal remodeling in human retinitis pigmentosa

Jones

Pfeiffer

Ferrell

et al. 2016

Experimental Eye Research

281

254

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Retinitis Pigmentosa (RP) in the human is a progressive, currently irreversible neural degenerative disease usually caused by gene defects that disrupt the function or architecture of the photoreceptors. While RP can initially be a disease of photoreceptors, there is increasing evidence that the inner retina becomes progressively disorganized as the outer retina degenerates. These alterations have been extensively described in animal models, but remodeling in humans has not been as well characterized. This study, using computational molecular phenotyping (CMP) seeks to advance our understanding of the retinal remodeling process in humans. We describe cone mediated preservation of overall topology, retinal reprogramming in the earliest stages of the disease in retinal bipolar cells, and alterations in both small molecule and protein signatures of neurons and glia. Furthermore, while Müller glia appear to be some of the last cells left in the degenerate retina, they are also one of the first cell classes in the neural retina to respond to stress which may reveal mechanisms related to remodeling and cell death in other retinal cell classes. Also fundamentally important is the finding that retinal network topologies are altered. Our results suggest interventions that presume substantial preservation of the neural retina will likely fail in late stages of the disease. Even early intervention offers no guarantee that the interventions will be immune to progressive remodeling. Fundamental work in the biology and mechanisms of disease progression are needed to support vision rescue strategies.

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Section: 0 Resultsmentioning

confidence: 99%

Retinal remodeling in human retinitis pigmentosa

Jones

Pfeiffer

Ferrell

et al. 2016

Experimental Eye Research

281

254

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“…To explore synaptic contacts between photoreceptor cells and ON rod bipolar cells in the OPL, we marked with antibodies against the protein Bassoon, a component of synaptic ribbons of both cone pedicles and rod spherules [57]. Double immunostaining for α-PKC and Bassoon evidenced the contact between the axon terminals of photoreceptor and bipolar cell dendrites (Fig 6A and 6B; arrows).…”

Section: Resultsmentioning

confidence: 99%

Controlled delivery of tauroursodeoxycholic acid from biodegradable microspheres slows retinal degeneration and vision loss in P23H rats

et al. 2017

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Successful drug therapies for treating ocular diseases require effective concentrations of neuroprotective compounds maintained over time at the site of action. The purpose of this work was to assess the efficacy of intravitreal controlled delivery of tauroursodeoxycholic acid (TUDCA) encapsulated in poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres for the treatment of the retina in a rat model of retinitis pigmentosa. PLGA microspheres (MSs) containing TUDCA were produced by the O/W emulsion-solvent evaporation technique. Particle size and morphology were assessed by light scattering and scanning electronic microscopy, respectively. Homozygous P23H line 3 rats received a treatment of intravitreal injections of TUDCA-PLGA MSs. Retinal function was assessed by electroretinography at P30, P60, P90 and P120. The density, structure and synaptic contacts of retinal neurons were analyzed using immunofluorescence and confocal microscopy at P90 and P120. TUDCA-loaded PLGA MSs were spherical, with a smooth surface. The production yield was 78%, the MSs mean particle size was 23 μm and the drug loading resulted 12.5 ± 0.8 μg TUDCA/mg MSs. MSs were able to deliver the loaded active compound in a gradual and progressive manner over the 28-day in vitro release study. Scotopic electroretinografic responses showed increased ERG a- and b-wave amplitudes in TUDCA-PLGA-MSs-treated eyes as compared to those injected with unloaded PLGA particles. TUDCA-PLGA-MSs-treated eyes showed more photoreceptor rows than controls. The synaptic contacts of photoreceptors with bipolar and horizontal cells were also preserved in P23H rats treated with TUDCA-PLGA MSs. This work indicates that the slow and continuous delivery of TUDCA from PLGA-MSs has potential neuroprotective effects that could constitute a suitable therapy to prevent neurodegeneration and visual loss in retinitis pigmentosa.

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“…OCT has become one of the most important tools in Ophthalmology, providing clinically relevant images with a clear histological correlation. It has also been an important tool in the investigation of therapies in animal models of neurodegenerative retinal diseases 28,29 . After the introduction of the SD-OCT, several studies have looked for the relationship between visual outcomes, after different pathologies and treatments, and the status of the outer hyperreflective bands in the human retina.…”

Section: Discussionmentioning

confidence: 99%