Genetic control of retinal ganglion cell projections

Abstract

We have assessed the effects of 15 pigmentation mutations on the development of retinal ganglion cell projections in mice in two ways: (1) by analyzing the pattern of innervation of the ipsilateral lateral geniculate nucleus as mapped in autoradiograms of brains of animals killed 12 days after intravitreal injection of 3H-proline into one eye and (2) by determining the ratio of axonally transported radioactive protein in the contralateral and ipsilateral optic tracts after similar intravitreal injections. Analysis of the ratio of transported protein in the two optic tracts provides a new and useful assay of the degree of decussation in experimental animals. The effects of the mutations on eye pigmentation, whole eye melanin content and relative tyrosinase activity also were examined. The degree of ipsilateral innervation generally correlates with the degree of pigmentation of the retinal pigment epithelium and with tyrosinase activity. However, discrepancies have been found in ch and ce mutants. In these animals the pigment epithelium is well pigmented, and the area of ipsilateral innervation in the lateral geniculate nucleus is extensive, despite a high ratio of label in contralateral to ipsilateral optic tracts and low tyrosinase activity. Furthermore, mice heterozygous for the c2J allele have pigmentation and optic projections that are normal even though tyrosinase is reduced to 40% of normal. The few anomalous results suggest that alternative or additional factors may control optic axon projections.

The distribution of melanin in the developing optic cup and stalk and its relation to cellular degeneration

“…The important and interesting relationship here is that a chiasmatic abnormality is found in association with a number of different genotypes, each of which produces pigment abnormalities by a distinct mechanism. Genes that produce their effects upon melanin by acting at quite distinct phases of pigment production or packaging also produce chiasmatic abnormalities (Sanderson et al, 1974;Wise and Lund, 1976;LaVail et al, 1978;Guillery et al, 1975Guillery et al, , 1979. Thus, one cannot postulate a single common cause producing both the pathway abnormality and the pigment abnormality by mechanisms that are otherwise independent, nor can one consider that the chiasmatic abnormality may produce the pigment abnormality: the spatiotemporal relationships are wrong.…”

“…A second, rather tentative argument for focusing attention upon the process of pigment cell degeneration rather than synthesis can be derived from consideration of the Chediak-Higashi syndrome. The evidence that there may be a pathway abnormality associated with this syndrome (Spencer and Hogan, 1960;Witkop, 1971;LaVail et al, 1978;Sanderson et al, 1974;Guillery et al, 1979) possibly implicates melanin breakdown or release in the production of the neural abnormality because the syndrome shows a general abnormality of lysosomal mechanisms and of melanosome structure (Witkop, 1971;Kramer et al, 1977).…”

“…' Our initial interest in the melanin arose from the observation that many individuals having abnormally low amounts of melanin in the retinal pigment epithelium also show a chiasmatic misrouting of some retinofugal axons. Since many different genes that produce melanin abnormalities, and that do so by a variety of different cellular mechanisms, also produce a chiasmatic abnormality (Sanderson et al, 1974;Wise and Lund, 1976;LaVail et al, 1978;Guillery et al, 1975Guillery et al, , 1979, one is led to conclude that the pigment itself is associated very closely with the mechanisms producing the pathway abnormality.…”

Axonal Transport and Sorting of Herpes Simplex Virus Components in a Mature Mouse Visual System

“…However, we did find HSV antigen on Western blots in the samples of the hypothalamus at 2 to 5 days after infection (data not shown). Some of the retina ganglion cells send an axon collateral branch to innervate neurons located in the suprachiasmatic nucleus of the hypothalamus (14,18). We limited the dissection to the portion of the optic pathway which was not in direct contact with these hypothalamic nuclei (see Fig.…”

Contrast Sensitivity Function of the Albino Rat Determined Electrophysiologically

“…The anomainus visual pathways produced by albinism are already well known. Many papas describe [he misrouted fibers of the ipsilateral projections (Drager & Olsen, 1980;Guillery, ¡974;Lund, 1965) andlink [bis [o [he loss of pigmentation (LaVail, Nixon, &Sidman, 1978;Sanderson, Guillcry, & Shackelford, 1974 In the past few years, con[roversy has arisen abou[ a possible night blindness ¡u albino rodents (Balkema, 1988 (Silveira, Heywood, & Cowey, 1987 …”