Closer look at lactose-mediated support of retinal morphogenesis.

We have previously shown in intact isolated eye rudiments from Xenopus laevis that lactose, but not mannose, permits the formation of organized photoreceptor outer segments in the absence of the retinal pigment epithelium (RPE). The purpose of this study was to determine, using electron microscopic analysis, the key ultrastructural differences between healthy retinas, lactose-protected retinas, and retinas that developed aberrantly to reveal which subcellular structures were exclusively present in healthy retinas. Filamentous actin was also localized in retinas to determine its distribution under the various conditions. In healthy retinas, calycal processes extending approximately three-fourths of the length of the outer segment surrounded highly organized photoreceptor outer segments. Adherens junctions were localized between adjacent photoreceptors and Müller cells at the outer limiting membrane. In addition, Müller cells possessed apical processes that extended for a short distance beyond the adherens junctions. These fine cytoarchitectural details were missing in retinas that completed differentiation in the absence of the RPE; both calycal and apical processes were no longer present and adherens junctions were sparsely intermittent. Müller cells appeared atrophic. Similarly, mannose promoted none of the fine cytoarchitectural details of the retina. Lactose, however, supported the formation of the proper subcellular cytoarchitecture of both photoreceptor and Müller cells. These results suggest that these subcellular structures may be fundamental for the proper assembly and stability of organized outer segments and are necessary to allow for normal cytogenesis of the outer retina.

Lactose promotes organized photoreceptor outer segment assembly and preserves expression of photoreceptor proteins in retinal degeneration.

PURPOSE: We have previously shown that lactose promotes the proper assembly of photoreceptor outer segments in the absence of the retinal pigment epithelium (RPE). The purpose of this study was to determine if the difference between organized and disorganized membranes was a variation in the amounts of two structural proteins, opsin and rds/peripherin. METHODS: Eye rudiments were dissected from Xenopus laevis embryos and the RPE was removed prior to culturing in the following media: Niu-Twitty medium; Niu-Twitty with mannose; Niu-Twitty with lactose. Controls included retinas that matured in vitro with an adherent RPE. Photoreceptor ultrastructure was evaluated with emphasis on outer segment membrane organization. The relative amounts of opsin and rds/ peripherin, two outer segment-specific proteins, were determined, as were their immunolabeling patterns. RESULTS: In control retinas, outer segments were composed of stacked, flattened membranous saccules. Opsin labeling of rod outer segments was very dense, indicative of normally organized disc membranes, and rds/peripherin labeling was heavy at the outer segment disc periphery and incisures. In the absence of the RPE, a whorl-like profile of outer segments is present in what would be the sub-retinal space. Opsin immunolabeling was patchy and disorganized. Immunolabeling of rds/peripherin was present, but in a disorderly array. Mannose showed no protective effect. In contrast, lactose promoted the formation of organized outer segments and allowed for near normal expression of both photoreceptor markers. In retinas with disorganized outer segments, the expression of opsin is downregulated while the expression of rds/peripherin is maintained or upregulated. CONCLUSIONS: Lactose protects against the retinal degeneration induced by RPE removal by preserving the outer segment structure and the photoreceptor immunolabeling patterns. It also maintains constant the relative amounts of opsin and rds/peripherin. It is possible that in degenerating retinas, photoreceptors upregulate rds/peripherin expression in attempt to provide additional support for the proper folding of nascent membranes, however this is insufficient to permit organization of the photoreceptor outer segments. Our results suggest that rescue-effect of lactose is mediated by a non-rds/peripherin related mechanism.

Alcoholic fathering and its relation to child's intellectual development: a pilot investigation.

In this study, the relationship between being raised by an alcoholic father and intellectual and academic achievement of the child were investigated. One hundred children of non-alcoholic mothers, 50 of whom had alcoholic fathers and 50 of whom had non-alcoholic fathers, were administered age-appropriate IQ, developmental, and achievement tests. Analysis of covariance revealed significant relationships between alcoholic fathering and IQ and achievement scores, independent of a number of possibly confounding variables. When children with alcoholic biological fathers were excluded, a relationship between IQ and alcoholic fathering persisted. Thus children raised by alcoholic fathers are a population at risk, in need of further scientific and clinical attention.