Inherited Retinal Dystrophy: Primary Defect in Pigment Epithelium Determined with Experimental Rat Chimeras

Mullen, Richard; LaVail, Matthew M.

doi:10.1126/science.1265483

Cited by 473 publications

(211 citation statements)

References 16 publications

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“…Outer segment phagocytosis is essential for retina function as defects result in photoreceptor cell death and progressive retinal degeneration much like that seen in Usher patients (Mullen and La Vail 1976). Shaker-1 retinal epithelia which lack myosin-VIIa exhibit normal levels of outer segment binding and phagosome formation, however phagosomes containing ROSs accumulate in apical regions because their transport to basal regions, where digestion is thought to occur, is inhibited (Gibbs et al 2003).…”

Section: Discussionmentioning

confidence: 99%

The unconventional myosin-VIIa associates with lysosomes

Soni

Warren

Bucci

et al. 2005

Cell Motil. Cytoskeleton

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Mutations in the myosin-VIIa (MYO7a) gene cause human Usher disease, characterized by hearing impairment and progressive retinal degeneration. In the retina, myosin-VIIa is highly expressed in the retinal pigment epithelium, where it plays a role in the positioning of melanosomes and other digestion organelles. Using a human cultured retinal pigmented epithelia cell line, ARPE-19, as a model system, we have found that a population of myosin-VIIa is associated with cathepsin D-and Rab7-positive lysosomes. Association of myosin-VIIa with lysosomes was Rab7 independent, as dominant negative and dominant active versions of Rab7 did not disrupt myosin-VIIa recruitment to lysosomes. Association of myosin-VIIa with lysosomes was also independent of the actin and microtubule cytoskeleton. Myosin-VIIa copurified with lysosomes on density gradients, and fractionation and extraction experiments suggested that it was tightly associated with the lysosome surface. These studies suggest that myosin-VIIa is a lysosome motor.

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Section: Discussionmentioning

confidence: 99%

The unconventional myosin-VIIa associates with lysosomes

Soni

Warren

Bucci

et al. 2005

Cell Motil. Cytoskeleton

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“…Studies on Royal College of Surgeons (RCS) rats also support this finding. In these, there is a genetic defect that renders the pigmented epithelium incapable of phagocytizing photoreceptor outer segments (Young & Bok 1969;Mullen & LaVail 1976). The photoreceptors develop normally until the outer segments begin to differentiate.…”

Section: Discussionmentioning

confidence: 99%

Survival of long‐term retinal cell transplants

Sharma

Bergström

Zucker

et al. 2000

Acta Ophthalmologica Scandinavica

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ABSTRACT.Purpose: If retinal cell transplants are to be used in the management of retinal degeneration, they will need to survive in the eye for long time. This study assesses the fate of neural retinal transplants in the eye after long survival times. Methods: Fragmented pieces of neural retinas from embryonic day 15 rabbits were transplanted to the subretinal space of adult animals of the same strain. The transplants were allowed to survive for up to 583 days prior to sacrifice and light microscopic examination. Results: In most grafts, both neural and glial cells survived, however, some of the grafts seemed to contain predominantly glial cells. Only when the photoreceptors in the graft were apposed to the host pigmented epithelium did they survive. Otherwise, the neuronal components of the grafts were largely cells typically found in the inner retina. The long-term transplants were much thinner than short-term ones. Even after long survival times, the transplants lacked vascularization. No inflammatory cells were seen in or around the grafts. Conclusion:The results suggest that the cells of the inner retina survive for long periods after transplantation, but the photoreceptor cells seem to need the support of the host pigmented epithelium for long-term survival. It may therefore be important to have a transplantation technique where the graft photoreceptors can be placed in apposition with the host pigment epithelium.

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“…Activity of the Mer tyrosine kinase receptor MerTK is essential for efficient engulfment of POS by RPE in vivo and in vitro (Mullen and LaVail, 1976;Edwards and Szamier, 1977) Despite its importance, mechanisms of MerTK activation and MerTK downstream signaling target proteins in RPE are still largely obscure. Retinal ligands of MerTK have not yet been conclusively identified.…”

Section: Role Of Mertk Activation In Rpe Phagocytosismentioning

confidence: 99%

Mertk Activation During RPE Phagocytosis in Vivo Requires αVβ5 Integrin

Finnemann

Nandrot

Advances in Experimental Medicine and Biology

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Inherited Retinal Dystrophy: Primary Defect in Pigment Epithelium Determined with Experimental Rat Chimeras

Cited by 473 publications

References 16 publications

The unconventional myosin-VIIa associates with lysosomes

The unconventional myosin-VIIa associates with lysosomes

Survival of long‐term retinal cell transplants

Mertk Activation During RPE Phagocytosis in Vivo Requires αVβ5 Integrin

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