A newly discovered pathway of melanin formation in cultured retinal pigment epithelium of cattle

Abstract

According to a recent hypothesis the melanin granules in the retinal pigment epithelium of mammals originate from photosensory membrane degradation. To test this hypothesis the retinal pigment epithelium of cattle was kept in tissue culture and exposed to gold-labelled rod outer segments. Gold granules were later detected inside phagosomes, melanosomes and mature melanin granules. Tyrosinase, the key enzyme in melanogenesis, was additionally localized inside phagosomes. These results indicate that in cultured retinal pigment epithelium the matrix of the melanosome can originate from phagosomes. Therefore, the melanosome is a specialized lysosome.

Subretinal Injection of Rod Outer Segments Leads to an Increase in the Number of Early-Stage Melanosomes in Retinal Pigment Epithelial Cells

“…Tyrosinase has been found in the adult RPE of cattle [5] and in cultivated RPE cells [6]. Furthermore, it was demonstrated that melanogenesis takes place in cultivated RPE cells of cattle, following feeding with rod outer segments (ROS) [6]. These findings are consistent with the study of Zhu et al [7], who found that adult RPE cells can produce new melanin.…”

“…In the RPE cells we found very few undigested ROS in phagolysosomes ( fig. 2), showing that the ROS of the cattle were decomposed by the RPE cells of the rats as found in vitro [6]. As shown in figure 3 and table 1, we found an increase in the number of early-stage melanosomes and small melanin granules in the eyes with ROS injection compared to eyes without injection.…”

“…The methods for the isolation of ROS [6,12] and the injection into the subretinal space [10][11][12] are established methods and the preservation of the membrane structure of the isolated ROS at the time of injection has been shown before [6].…”

“…The amino acid tyrosine from which melanin is synthesized is present as are the required enzymes. Tyrosinase has been found in the adult RPE of cattle [5] and in cultivated RPE cells [6]. Furthermore, it was demonstrated that melanogenesis takes place in cultivated RPE cells of cattle, following feeding with rod outer segments (ROS) [6].…”

Molecular and Functional Characterization of a Unique Rab Protein, RABRP1, Containing the WDIAGQE Sequence in a GTPase Motif

“…These data therefore suggest that RABRP1 functions in the vesicle transport pathway toward lysosomes and/or its related structures. Recently, in mammalian pigment cells (melanocytes), it has been suggested that melanosomes, organelles containing the melanin pigment, are specialized forms of late endosomes or lysosomes, and are formed through a similar pathway to that of lysosomes (Jimbow et al, 1997;Schraermeyer and Stieve, 1994;Vijayasaradhi et al, 1995). Furthermore, in Drosophila, several kinds of proteins required for vesicle traffic to lysosomes are also essential for biogenesis of pigment granules: garnet gene product, which functions in the delivery of proteins to pigment granules, was identified as the δ-subunit of the AP-3 adaptor complex that was involved in the Golgi-to-lysosome pathway (Cowles et al, 1997;Le Borgne et al, 1998;Ooi et al, 1997;Simpson et al, 1997).…”