Dorsal retinal pigment epithelium differentiates as neural retina in the Microphthalmia (mi/mi) mouse

PURPOSE. Microphthalmia, a bHLH-zip transcription factor associated with th e onset and maintenance of pigmentation, identifies the retinal pigment epi thelial (RPE) compartment during optic vesicle and optic cup development. T o determine a role for microphthalmia (mi) during eye development, the effe cts of an mi loss of function mutation on RPE and neural retinal were inves tigated in the mi/mi mouse. METHODS. A series of embryonic and postnatal mi/mi and wild-type eyes were sectioned and labeled with neural retina- and RPE cell type-specific antibo dies. Photoreceptor loss was quantified by counting the number of photorece ptor nuclei spanning the outer nuclear layer throughout postnatal retinal d evelopment. RESULTS. Early neural retinal differentiation is not affected in the mi/mi mouse. The mi/mi ventral retinal pigment epithelial layer begins to develop normally, but does not pigment or attain a differentiated cuboidal morphol ogy. The dorsal region of mi/mi retinal pigment epithelium expands and form s an ectopic retina, which develops all major retinal cell types along a si milar time course as the wild type. After birth, mi/mi photoreceptors begin to form rosettes, outer segments fail to elongate, and over an extended ti me period, the retina degenerates. CONCLUSIONS. Together these results suggest that early retinal development can proceed normally in the mi/mi mutant, but later retinal histogenesis is dependent on the presence of a differentiated retinal pigment epithelium. Most importantly, loss of mi function permits a change in cell fate from RP E to retina in the dorsal eye.