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Editors Selection IGR 17-4
Basic research: Embryonic medium and RGC
Comment by Keith Martin on:
16806 Characterization of early retinal progenitor microenvironment: Presence of activities selective for the differentiation of retinal ganglion cells and maintenance of progenitors, Hegde GV; James J; Das AV et al., Experimental Eye Research, 2007; 84: 577-590
Successful regeneration or replacement of retinal ganglion cells (RGC) lost due to disease will probably require us to understand in detail the mechanisms by which RGC differentiation is controlled. Much can be learned from the study of how RGC arise during normal development. RGCs develop in a complex millieu that changes over relatively short periods of time and thus the exact microenvironment to which cells are exposed is difficult to characterize and study.
RGC are usually the first retinal cells to differentiate, regardless of species. In a very interesting study, Hegde et al. (71) hypothesized that the retinal microenvironment early in development is likely to contain factors that are permissive for RGC development, inhibitory for development of later-born retinal neurons and permissive for the maintenance of a pool of progenitor cells. They studied the effect of conditioned medium from embryonic day 3 (E3) on the growth of retinal neurospheres. The authors also compared the effects of the heat labile and heat stable components of the medium, above and below an arbitrary molecular weight cut-off of 30kDa. The authors found evidence of factors that enhance RGC differentiation, inhibit late retinal neurons and maintain progenitors in different fractions of the medium. Separating the media into fractions by size and heat sensitivity is a fairly crude way to narrow down what the specific factors are, but the method nevertheless represents a good start in dissecting the highly complex control of RGC development.
One important point is that the paper addresses the control of stem cells by soluble factors (in conditioned media) but does not address signaling that requires cell-cell contact. Contact signals are almost certainly important retinal development, but assessing their importance will require a different type of experimental system.
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