Influence of tyrosinase levels on pigment accumulation in the retinal pigment epithelium and on the uncrossed retinal projection.
To study the relationship among tyrosinase activity, melanin production, and the routing of retinal ganglion cell (RGC) axons at the optic chiasm, we analysed mice with varying doses of the tyrosinase gene. These include the dark-eyed albino (Tyrc44H), a radiation-induced hypomorphic allele of tyrosinase; and transgenic mice carrying 1 or 2 alleles of a tyrosinase minigene on both wild-type (Tyr+) and albino (Tyrc) backgrounds. Melanization of the retinal pigment epithelium (RPE) occurred gradually even at <2% wild-type tyrosinase activity and was sensitive to tyrosinase activity up to <35% of wild-type levels, beyond which melanin synthesis appeared to be saturated. Overexpression of tyrosinase led to tyrosinase activity above wild type level, but did not increase melanin production. Although a loss of melanin because of a mutation in tyrosinase is associated with a decrease in the number of uncrossed fibers, elevating tyrosinase levels does not appear to cause an increase in the size of the uncrossed retinal projection. Our results suggest that replacing less than 35% of wild-type tyrosinase activity is sufficient to restore normal pigmentation of the RPE, and potentially, to allay visual defects.
Rachel
Rivka A
RA
Center for Neurobiology and Behaviour, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Mason
Carol A
CA
Beermann
Friedrich
F
D016115:Albinism, Oculocutaneous / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000378:metabolism / Q000648:ultrastructure; D002232:Carbocyanines; D005260:Female; D007839:Functional Laterality / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006197:Hair / Q000002:abnormalities / Q000254:growth & development / Q000378:metabolism; D008297:Male; D008543:Melanins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D014442:Monophenol Monooxygenase / Q000172:deficiency* / Q000235:genetics; D009900:Optic Nerve / Q000002:abnormalities* / Q000166:cytology / Q000254:growth & development; D010641:Phenotype; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000201:enzymology*; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism*; D014795:Visual Pathways / Q000002:abnormalities* / Q000166:cytology / Q000254:growth & development
C035005:3,3'-dihexadecylindocarbocyanine; D002232:Carbocyanines; D008543:Melanins; D014442:Monophenol Monooxygenase