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 serie s of reciprocal cellular interactions that determine the fate of the e ye 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 d emonstrated in vivo. Results: To investigate the role of RPE cells in eye development, we generated transgenic mice that carry the attenuate d diphtheria toxin-A gene; this transgene was driven by the promoter o f the gene encoding the tyrosinase-related protein-1, which is specifi cally 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 ab lation (embryonic day E10-11) resulted in disorganization of the retin al layer, immediate arrest of eye growth and subsequent eye resorption . A later ablation (E11.5-12.5) allowed the eye to be maintained durin g embryogenesis, but the laminar structure of the retina became disrup ted by the end of gestation, the vitreous failed to accumulate and adu lts were anophthalmic or severely microphthalmic. In some microphthalm ic eyes, a number of RPE cells escaped ablation and formed patches of pigmented cells; the laminar structure of the retina was maintained im mediately adjacent to such pigmented areas but disrupted elsewhere. In both cases - early or late ablation of the RPE - the retina appears t o be the primary affected tissue. Conclusions: We conclude that presen ce of the RPE is required for the normal development of the eye in viv o. Its presence early in development is necessary for the correct morp hogenesis of the neural retina. After the neural retina has started to differentiate, the RPE is still necessary, either directly or indirec tly, to maintain the organization of the retinal lamina.