Melanin Granules of Retinal Pigment Epithelium are Connected with the Lysosomal Degradation Pathway

Schraermeyer, Ulrich; Peters, Swaantje; Thumann, Gabriele; Kociok, Norbert; Heimann, Klaus

doi:10.1006/exer.1998.0596

Cited by 91 publications

(74 citation statements)

References 29 publications

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“…First, an increase of melanin, melanolysosomes, or melanolipofuscin content in the RPE cell may occur. Limited melanogenesis has been found in adults, 43 and as melanin is involved in photoreceptor outer segment phagocytosis, 44 an increase of melanogenesis as a response to increased phagocytosis of degenerating photoreceptors is feasible. 45 An increase of melanolysosomes and melanolipofuscin has been documented in degenerative diseases.…”

Section: Discussionmentioning

confidence: 99%

Lipofuscin- and melanin-related fundus autofluorescence visualize different retinal pigment epithelial alterations in patients with retinitis pigmentosa

Kellner

Weber

et al. 2008

Eye

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Aims To compare melanin-related nearinfrared fundus autofluorescence (FAF; NIA, excitation 787 nm, emission 4800 nm) with lipofuscin-related FAF (excitation 488 nm, emission 4500 nm) in retinitis pigmentosa (RP). Methods Thirty-three consecutive RP patients with different modes of inheritance were diagnosed clinically, with full-field ERG, and if possible with molecular genetic methods. FAF and NIA imaging were performed with a confocal scanning laser ophthalmoscope (Heidelberg Retina Angiograph 2). Results Rings of increased FAF were present within an area of preserved retinal pigment epithelium (RPE) at the posterior pole (31/33). Rings of increased NIA were located in the same region as rings of increased FAF. In contrast to FAF, NIA showed a precipitous decline of NIA peripheral to the ring. In larger areas of preserved NIA (11/31), pericentral and foveal NIA were of similar intensity with an area of lower NIA in between. In smaller areas of preserved NIA (20/31), NIA was homogeneous from the perifovea to the fovea. In one patient without a ring of increased FAF, NIA distribution was normal. In the remaining patient with severely advanced RP, no residual RPE as well as no FAF and NIA were detectable. Conclusion Characteristic features for FAF and NIA alterations in a heterogeneous group of RP patients indicate a common pathway of RPE degeneration. Patterns of NIA and FAF indicate different pathophysiologic processes involving melanin and lipofuscin. Combined NIA and FAF imaging will provide further insight into the pathogenesis of RP and noninvasive monitoring of future therapeutic interventions.

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Section: Discussionmentioning

confidence: 99%

Lipofuscin- and melanin-related fundus autofluorescence visualize different retinal pigment epithelial alterations in patients with retinitis pigmentosa

Kellner

Weber

et al. 2008

Eye

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“…Although melanosomes have not been shown definitively to have degradative properties, they are able to fuse with phagosomes and express many lysosomal hydrolases including β-glucuronidase, β-galactosidase, β-hexosaminidase and cathepsin B and L (Diment et al 1995). Fusion of phagosomes with melanosomes is most prominently observed in cells overloaded with ROS or undigestable products (Orlow 1995;Schraermeyer et al 1999). Recent studies show that a large fraction of myosin-VIIa in primary RPE cells is found on melanosomal membranes (Gibbs et al 2004).…”

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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“…Moreover, melanosomes have functional and structural similarities to lysosomes, and have been considered as indeed specialized lysosomes (Orlow, 1995;Schraermeyer et al, 1999;Ahn et al, 2008b Macrophages are key cellular components of the innate immune system. Following tissue injury or infection, macrophages exhibit an inflammatory phenotype and secrete pro-inflammatory mediators such as tumor necrosis factor, NO, and interleukin-1, which participate in the activation of various antimicrobial mechanisms (Murray and Wynn, 2011).…”

Section: Melanocytes and Adaptive Immunitymentioning

confidence: 99%