The changes of potassium currents in RCS rat Müller cell during retinal degeneration

Zhao, Tongtao; Li, YaoChen; Weng, Chuanhuang; Yin, Zhinan

doi:10.1016/j.brainres.2011.10.011

Cited by 14 publications

(13 citation statements)

References 29 publications

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“…The increase in GFAP labeling in all unimplanted RCS and S334ter-3 retinas compared to WT (images not shown) is consistent with previous reports on retinal remodeling during degeneration (Marc and Jones, 2003; Zhao et al, 2012). Importantly, GFAP labeling in and around the implant site was similar to distal areas, suggesting that the glial reaction was not augmented by the presence of the PVA.…”

Section: Discussionsupporting

confidence: 91%

Inner retinal preservation in rat models of retinal degeneration implanted with subretinal photovoltaic arrays

Light

Fransen

Adekunle

et al. 2014

Experimental Eye Research

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Photovoltaic arrays (PVA) implanted into the subretinal space of patients with retinitis pigmentosa (RP) are designed to electrically stimulate the remaining inner retinal circuitry in response to incident light, thereby recreating a visual signal when photoreceptor function declines or is lost. Preservation of inner retinal circuitry is critical to the fidelity of this transmitted signal to ganglion cells and beyond to higher visual targets. Post-implantation loss of retinal interneurons or excessive glial scarring could diminish and/or eliminate PVA-evoked signal transmission. As such, assessing the morphology of the inner retina in RP animal models with subretinal PVAs is an important step in defining biocompatibility and predicting success of signal transmission. In this study, we used immunohistochemical methods to qualitatively and quantitatively compare inner retinal morphology after the implantation of a PVA in two RP models: the Royal College of Surgeons (RCS) or transgenic S334ter-line 3 (S334ter-3) rhodopsin mutant rat. Two PVA designs were compared. In the RCS rat, we implanted devices in the subretinal space at 4 weeks of age and histologically examined them at 8 weeks of age and found inner retinal morphology preservation with both PVA devices. In the S334ter-3 rat, we implanted devices at 6 to 12 weeks of age and again, inner retinal morphology was generally preserved with either PVA design 16 to 26 weeks post implantation. Specifically, the length of rod bipolar cells and numbers of cholinergic amacrine cells were maintained along with their characteristic inner plexiform lamination patterns. Throughout the implanted retinas we found nonspecific glial reaction, but none showed additional glial scarring at the implant site. Our results indicate that subretinally implanted PVAs are well-tolerated in rodent RP models and that the inner retinal circuitry is preserved, consistent with our published results showing implant-evoked signal transmission.

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Section: Discussionsupporting

confidence: 91%

Inner retinal preservation in rat models of retinal degeneration implanted with subretinal photovoltaic arrays

Light

Fransen

Adekunle

et al. 2014

Experimental Eye Research

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“…The expression of GFAP in the Müller cells of control rats was not detected until p90 (Figure 1C–1C2) [34, 35]. These data suggested that retinal degeneration stimulates Müller cell de-differentiation into multipotent retinal progenitors at the early stages of degeneration in RCS-p+ rats, but these de-differentiated cells seem to become committed to a gliotic phenotype at the later stages of degeneration.…”

Section: Resultsmentioning

confidence: 96%

Lin28B promotes Müller glial cell de-differentiation and proliferation in the regenerative rat retinas

et al. 2016

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Retinal regeneration and repair are severely impeded in higher mammalian animals. Although Müller cells can be activated and show some characteristics of progenitor cells when injured or under pathological conditions, they quickly form gliosis scars. Unfortunately, the basic mechanisms that impede retinal regeneration remain unknown. We studied retinas from Royal College of Surgeon (RCS) rats and found that let-7 family molecules, let-7e and let-7i, were significantly overexpressed in Müller cells of degenerative retinas. It demonstrated that down-regulation of the RNA binding protein Lin28B was one of the key factors leading to the overexpression of let-7e and let-7i. Lin28B ectopic expression in the Müller cells suppressed overexpression of let-7e and let-7i, stimulated and mobilized Müller glia de-differentiation, proliferation, promoted neuronal commitment, and inhibited glial fate acquisition of de-differentiated Müller cells. ERG recordings revealed that the amplitudes of a-wave and b-wave were improved significantly after Lin28B was delivered into the subretinal space of RCS rats. In summary, down-regulation of Lin28B as well as up-regulation of let-7e and let-7i may be the main factors that impede Müller cell de-differentiation and proliferation in the retina of RCS rats.

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“…Maintenance of normal electrophysiology and the absence of Müller cell proliferation are highly indicative of conservative reactive gliosis in the rd/rd retina during stages of active photoreceptor degeneration. In the RCS rat, however, changes in K þ currents occurred in very late stages of degeneration, suggesting the conservative gliosis can convert to proliferative gliosis in animal models of retinitis pigmentosa (Zhao et al, 2012). Additional cell recordings are needed to determine if electrophysical changes occur in rd/rd Müller cells after complete photoreceptor loss.…”

Section: Müller Cell Electrophysiologymentioning

confidence: 96%

Early remodeling of müller cells in the rd/rd mouse model of retinal dystrophy

Chua

Nivison‐Smith

Fletcher

et al. 2013

J of Comparative Neurology

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We studied the anatomical remodeling and gliosis of retinal Müller cells in the rd/rd mouse model of photoreceptor degeneration. A computational calculation of glutamine synthetase immunoreactivity was developed so we could specifically quantify changes in Müller cell anatomy between control mice (C57Bl/6) and the dystrophic strain. We found no change in the number of Müller cell somata between mice strains, indicating no cell proliferation as a function of development and degeneration. The retinal area occupied by the total Müller cell body (soma and processes) was significantly less in the rd/rd mouse retina compared with control mice. When only the outer retina was considered, we found rd/rd Müller cell processes were dramatically reduced during the cone phase of photoreceptor degeneration. However, at older ages an increase in Müller cell processes was seen. Conversely, glial fibrillary acidic protein (GFAP) expression showed a significant increase during cone degeneration followed by a reduction in older ages. Müller cell electrophysiology, particularly K(+) currents and membrane potential, was similar between rd/rd and control Müller cells during cone degeneration. Together, these results show that glial remodeling in the rd/rd retina follows separate phases-an initial conservative glial response involving the loss of Müller cells processes, hyperexpression of GFAP, and preservation of normal electrophysiology followed by an active growth of Müller cell processes, glial seal formation, and attenuation of GFAP expression after complete photoreceptor loss.

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The changes of potassium currents in RCS rat Müller cell during retinal degeneration

Cited by 14 publications

References 29 publications

Inner retinal preservation in rat models of retinal degeneration implanted with subretinal photovoltaic arrays

Inner retinal preservation in rat models of retinal degeneration implanted with subretinal photovoltaic arrays

Lin28B promotes Müller glial cell de-differentiation and proliferation in the regenerative rat retinas

Early remodeling of müller cells in the rd/rd mouse model of retinal dystrophy

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