Human ocular melanocytes and retinal pigment epithelial cells differ in their melanogenic properties in vivo and in vitro.

Smith-Thomas, L.C.; Richardson, P. S.; Thody, AJ; Graham, Alison; Palmer, Ian R.; Flemming, Lars; Parsons, M A; Rennie, IG; MacNeil, Sheila

doi:10.1016/s0002-9394(14)71113-4

Cited by 19 publications

(24 citation statements)

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“…Immunocytochemical staining to detect newly formed (immature) melanosomes with antibody HMB-45 in cultures of various donors at different passages revealed that melanogenesis is occurring within the cells. This confirms previous reports by Smith-Thomas et al [29], who observed that choroidal melanocytes can produce new melanin throughout life, in contrast to the neighbouring retinal pigment epithelium. It can be concluded from these results that the cultured NHCMs are capable of producing melanin and melanosomes in vitro, although they do not show active melanogenesis in vivo.…”

Section: Discussionsupporting

confidence: 93%

Serum-free cultivation of adult normal human choroidal melanocytes

Valtink

Engelmann

2007

Graefes Arch Clin Exp Ophthalmol

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Section: Discussionsupporting

confidence: 93%

Serum-free cultivation of adult normal human choroidal melanocytes

Valtink

Engelmann

2007

Graefes Arch Clin Exp Ophthalmol

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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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“…Melanin synthesis begins in the embryonic RPE, but controversy remains over whether there is a low level of melanin synthesis in the adult RPE. Several studies have reported an absence of tyrosinase and/or tyrosinase-related protein expression in adult RPE (Miyamoto and Fitzpatrick, 1957;Smith-Thomas et al, 1996). However, tyrosinase activity has been detected in extracts from adult RPE (Dryja et al, 1978;Varela et al, 1995), and tyrosinase expression/activity was detected in cultured adult RPE cells (Basu et al, 1983;Dorey et al, 1990), and it was increased after incubation with rod outer segments (Schraermeyer et al, 2006).…”

Section: The Timing Of Melanosome Formation In Ocular Tissuesmentioning

confidence: 99%

Melanosome Maturation Defect in Rab38-deficient Retinal Pigment Epithelium Results in Instability of Immature Melanosomes during Transient Melanogenesis

Lopes

Wasmeier

Seabra

et al. 2007

MBoC

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Pathways of melanosome biogenesis in retinal pigment epithelial (RPE) cells have received less attention than those of skin melanocytes. Although the bulk of melanin synthesis in RPE cells occurs embryonically, it is not clear whether adult RPE cells continue to produce melanosomes. Here, we show that progression from pmel17-positive premelanosomes to tyrosinase-positive mature melanosomes in the RPE is largely complete before birth. Loss of functional Rab38 in the "chocolate" (cht) mouse causes dramatically reduced numbers of melanosomes in adult RPE, in contrast to the mild phenotype previously shown in skin melanocytes. Choroidal melanocytes in cht mice also have reduced melanosome numbers, but a continuing low level of melanosome biogenesis gradually overcomes the defect, unlike in the RPE. Partial compensation by Rab32 that occurs in skin melanocytes is less effective in the RPE, presumably because of the short time window for melanosome biogenesis. In cht RPE, premelanosomes form but delivery of tyrosinase is impaired. Premelanosomes that fail to deposit melanin are unstable in both cht and tyrosinase-deficient RPE. Together with the high levels of cathepsin D in immature melanosomes of the RPE, our results suggest that melanin deposition may protect the maturing melanosome from the activity of lumenal acid hydrolases.

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Human ocular melanocytes and retinal pigment epithelial cells differ in their melanogenic properties in vivo and in vitro.

Cited by 19 publications

References 0 publications

Serum-free cultivation of adult normal human choroidal melanocytes

Serum-free cultivation of adult normal human choroidal melanocytes

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

Melanosome Maturation Defect in Rab38-deficient Retinal Pigment Epithelium Results in Instability of Immature Melanosomes during Transient Melanogenesis

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