Reorganization of actin microfilaments and microtubules in regenerating retinal pigment epithelium

Korte, Gary E.; Mrowiec, Ewa; Landzberg, Kim S.; Youssri, Ayman I.

doi:10.1016/s0014-4835(05)80039-9

Cited by 12 publications

(5 citation statements)

References 13 publications

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“…RPE shedding structures are associated with apical ejection of a central dead or dying RPE cell (Nagai and Kalnins, 1996). Enlarged cells with irregular borders at the central edge of the transition zone may be similar to those reported at the boundary of RPE atrophy in retinal cross sections and in RPE/choroid/sclera flat mounts of sodium iodate-injured mouse and rabbit eyes (Kiuchi et al, 2002; Korte et al, 1995). These observations lead us to propose an initial injury response in which dead or dying RPE cells are shed by a “purse string” closure process characteristic of epithelial monolayers (Garcia-Fernandez et al, 2009).…”

Section: Discussionsupporting

confidence: 78%

Enhanced retinal pigment epithelium regeneration after injury in MRL/MpJ mice

Xia

Krebs

Kaushal

et al. 2011

Experimental Eye Research

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Regenerative medicine holds the promise of restoring cells and tissues that are destroyed in human disease, including degenerative eye disorders. However, development of this approach in the eye has been limited by a lack of animal models that show robust regeneration of ocular tissue. Here, we test whether MRL/MpJ mice, which exhibit enhanced wound healing, can efficiently regenerate the retinal pigment epithelium (RPE) after an injury that mimics the loss of this tissue in age-related macular degeneration. The RPE of MRL/MpJ and control AKR/J mice was injured by retro-orbital injection of sodium iodate at 20 mg/kg body weight, which titration studies indicated was optimal for highlighting strain differences in the response to injury. Five days after sodium iodate injection at this dose, electroretinography of both strains revealed equivalent retinal responses that were significantly reduced compared to untreated mice. At one and two months post-injection, retinal responses were restored in MRL/MpJ but not AKR/J mice. Brightfield and fluorescence microscopy of eyecup cryosections indicated an initial central loss of RPE cells and RPE65 immunostaining in MRL/MpJ and AKR/J mice, with preservation of peripheral RPE. Phalloidin staining of posterior eye wholemounts confirmed this pattern of RPE loss, and revealed a transition region characterized by RPE cell shedding and restructuring in both strains, suggesting a similar initial response to injury. At one month post-injection, central RPE cells, RPE65 immunostaining and phalloidin staining were restored in MRL/MpJ but not AKR/J mice. BrdU incorporation was observed throughout the RPE of MRL/MpJ but not AKR/J mice after one month of administration following sodium iodate treatment, consistent with RPE proliferation. These findings provide evidence for a dramatic regeneration of the RPE after injury in MRL/MpJ mice that supports full recovery of retinal function, which has not been observed previously in mammalian eyes. This model should prove useful for understanding molecular mechanisms that underlie regeneration, and for identifying factors that promote RPE regeneration in age-related macular degeneration and related diseases.

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Section: Discussionsupporting

confidence: 78%

Enhanced retinal pigment epithelium regeneration after injury in MRL/MpJ mice

Xia

Krebs

Kaushal

et al. 2011

Experimental Eye Research

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“…Each area has specific features that can be analyzed with fluorescent markers. Phalloidin labeling permitted us to observe morphologic changes in RPE cells resembling those described by Korte et al 25 using a chemical ablation model. These included the appearance of several mor-phologically distinct classes of RPE cells located at the edge of the regenerating epithelial monolayer that proliferate and migrate toward the center of the lesion.…”

Section: Iovsmentioning

confidence: 73%

A Novel Imaging Technique for Experimental Choroidal Neovascularization

Campos¹,

Amaral

et al. 2006

Invest. Ophthalmol. Vis. Sci.

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A novel imaging technique was developed that allows a three-dimensional reconstruction and measurement of laser-induced CNV lesions in rat choroid/RPE flatmounts. This technique provides excellent morphologic detail and facilitates the study of critical early events in CNV, including the rupture of Bruch's membrane and the formation of endothelial clusters before vessel formation. CNV complexes are labeled at an earlier stage and more reproducibly than with FITC-dextran perfusion, providing a more accurate preclinical evaluation of antiangiogenic molecules.

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“…The contractile filaments myosin I and II have also been detected in the RPE cells of various mammals and fish (Breckler and Burnside, 1994). The presence of actin in RPE cells has been reported in numerous in vitro and in vivo studies (e.g., Burnside, 1976;Burnside and Laties, 1979;Chaitin and Hall, 1983;Haley et al, 1983;Owaribe, 1988;Fuchs et al, 1991) and has been shown to reorganise during migration (e.g., Campochiaro and Glaser, 1986) and regeneration (Korte et al, 1995). Lastly, some in vitro studies have shown that the interaction of RPE cells with matrix may cause contraction of the RPE cell sheets (Verstraeten et al, 1992;Smith-Thomas et al, 1996), and RPE cells have also been shown to mediate collagen contraction in vitro (Yamakawa et al, 1989;Raymond and Thompson, 1990;Grisanti and Guidry, 1995).…”

Section: Discussionmentioning

confidence: 91%

Ganglion cell loss in RCS rat retina: A result of compression of axons by contracting intraretinal vessels linked to the pigment epithelium

et al. 1998

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In the dystrophic Royal College of Surgeons (RCS) rat retina, there is a progressive loss of photoreceptors. As a result, the retinal circulation becomes apposed to the retinal pigment epithelium (RPE) and neovascular formations develop. RPE and inner nuclear layer cells migrate along these vessels towards the retinal ganglion cell (RGC) layer. The retinal layers gradually become disrupted, and some of the RGC axon bundles involute into the retina. These bundles are always associated with blood vessels, and there is evidence of axon damage where they juxtapose. In wholemount preparations of dystrophic retinae (> or =6 months of age), abrupt changes are observed in the trajectory of RGC axon bundles, where they are crossed by circumferential vessels. Degenerative profiles can be seen at these locations. Visualisation of RGCs with Fluoro-gold shows wedge-shaped sectors in the dystrophic retina devoid of labelling, initially in the ventral retina but later spreading dorsally. It is hypothesised that the vessels supplying the neovascular formations contract and pull surface vessels into the retina, thus displacing any axon bundles that lie beneath them into the inner plexiform layer. The contractility may be an intrinsic property of the vessels or it may be conferred by the cells migrating along them. Axonal transport becomes blocked at the points of tension, thereby causing retrograde degeneration of the parent RGCs. Because RGC loss is also a feature of human retinitis pigmentosa, the RCS rat may provide a model to test interventions devised to prevent such loss following photoreceptor degeneration. This model also may be useful for testing methods designed to control blood vessel and matrix formation.

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Reorganization of actin microfilaments and microtubules in regenerating retinal pigment epithelium

Cited by 12 publications

References 13 publications

Enhanced retinal pigment epithelium regeneration after injury in MRL/MpJ mice

Enhanced retinal pigment epithelium regeneration after injury in MRL/MpJ mice

A Novel Imaging Technique for Experimental Choroidal Neovascularization

Ganglion cell loss in RCS rat retina: A result of compression of axons by contracting intraretinal vessels linked to the pigment epithelium

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