Albino mammals have profound
retinal abnormalities, including photoreceptor deficits and misrouted hemispheric pathways into the brain, demonstrating that
melanin or its precursors are required for normal
retinal development.
Tyrosinase, the primary
enzyme in
melanin synthesis commonly mutated in
albinism, oxidizes
l-tyrosine to l-
dopaquinone using
l-3,4-dihydroxyphenylalanine (
L-DOPA) as an intermediate product.
L-DOPA is known to signal cell cycle exit during
retinal development and plays an important role in the regulation of
retinal development. Here, we have mimicked
L-DOPA production by ectopically expressing
tyrosine hydroxylase in mouse albino retinal pigment epithelium cells.
Tyrosine hydroxylase can only oxidize
l-tyrosine to
L-DOPA without further progression towards
melanin. The resulting transgenic animals remain phenotypically albino, but their visual abnormalities are corrected, with normal photoreceptor numbers and hemispheric pathways and improved visual function, assessed by an increase of spatial acuity. Our results demonstrate definitively that only early
melanin precursors,
L-DOPA or its metabolic derivatives, are vital in the appropriate development of mammalian retinae. They further highlight the value of substituting independent but biochemically related
enzymes to overcome developmental abnormalities.