The retinal pigmented epithelium is required for development and maintenance of the mouse neural retina.
BACKGROUND
During development of the vertebrate eye, there is a series of reciprocal cellular interactions that determine the fate of the eye components. Although evidence from organ culture suggests that the retinal pigmented epithelium (RPE) organizes the laminar structure of the differentiated neural retina, no role has been identified for the RPE in early eye development, nor has the later function of RPE been demonstrated in vivo.


RESULTS
To investigate the role of RPE cells in eye development, we generated transgenic mice that carry the attenuated diphtheria toxin-A gene; this transgene was driven by the promoter of the gene encoding the tyrosinase-related protein-1, which is specifically expressed in pigment cells. Depending on the expression level of the transgene, the retinal epithelium was ablated before or after its differentiation into a pigmented cell layer. We show that an early ablation (embryonic day E10-11) resulted in disorganization of the retinal layer, immediate arrest of eye growth and subsequent eye resorption. A later ablation (E11.5-12.5) allowed the eye to be maintained during embryogenesis, but the laminar structure of the retina became disrupted by the end of gestation, the vitreous failed to accumulate the adults were anophthalmic or severely microphthalmic. In some microphthalmic eyes, a number of RPE cells escaped ablation and formed patches of pigmented cells; the laminar structure of the retina was maintained immediately adjacent to such pigmented areas but disrupted elsewhere. In both cases--early or late ablation of the RPE--the retina appears to be the primary affected tissue.


CONCLUSIONS
We conclude that presence of the RPE is required for the normal development of the eye in vivo. Its presence early in development is necessary for the correct morphogenesis of the neural retina. After the neural retina has started to differentiate, the RPE is still necessary, either directly or indirectly, to maintain the organization of the retinal lamina.
Raymond
S M
SM
MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK. ian@hgu.mrc.ac.uk
Jackson
I J
IJ
D000818:Animals; D002454:Cell Differentiation; D004167:Diphtheria Toxin / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000235:genetics; D010857:Pigment Epithelium of Eye / Q000196:embryology* / Q000502:physiology; D012160:Retina / Q000196:embryology* / Q000502:physiology
D004167:Diphtheria Toxin; D010446:Peptide Fragments; C029795:diphtheria toxin fragment A