Correction of retinal abnormalities found in albinism by introduction of a functional tyrosinase gene in transgenic mice and rabbits.
The factors that regulate normal retinal development remain obscure. However, it is known that elements in the retinal pigment epithelium are critical. When melanin is absent there is a reduction in rods, the central retina fails to develop fully and there is a systematic distortion in the chiasmatic projection to the brain. It has been demonstrated using transgenic mice that the chiasmatic abnormality is controlled by the tyrosinase gene, which is the key enzyme in melanin synthesis. Here we examine whether the two retinal deficits are regulated by this gene. We have examined the distribution of photoreceptors in an albino mouse strain in which a functional tyrosinase gene has been inserted and compared these transgenics with albino and wild type mice. In albinos, rod photoreceptors were reduced by approximately 30%, but were normal in the transgenics. Cone numbers were unchanged. Cell density in the ganglion cell layer was examined in transgenic rabbits, in which albinism had also been rescued with the tyrosinase gene. Normal rabbits have a steep gradient in cell density between central and peripheral retina. Cell density was abnormally low in the central retina in albinos, but normal in the transgenics. Hence, the tyrosinase gene is responsible for each of the retinal deficits associated with albinism. However, it is not clear whether this is due to the absence of melanin or whether the key agent is an associated cell product.
Jeffery
G
G
Institute of Ophthalmology, University College London, UK. g.jeffery@ucl.ac.uk
Brem
G
G
Montoliu
L
L
D016117:Albinism, Ocular / Q000235:genetics* / Q000473:pathology; D000818:Animals; D030801:Animals, Genetically Modified; D015316:Genetic Therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D014442:Monophenol Monooxygenase / Q000235:genetics*; D009897:Optic Chiasm / Q000002:abnormalities*; D010786:Photoreceptor Cells / Q000502:physiology; D011817:Rabbits; D012160:Retina / Q000002:abnormalities*; D012165:Retinal Ganglion Cells / Q000473:pathology*
D014442:Monophenol Monooxygenase