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Dorsal retinal pigment epithelium differentiates as neural retina in the microphthalmia (mi/mi) mouse
1Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, Connecticut, USA.
Purpose:
Microphthalmia, a bHLH-zip transcription factor associated with the onset and maintenance of pigmentation, identifies the retinal pigment epithelial (RPE) compartment during optic vesicle and optic cup development. To determine a role for microphthalmia (mi) during eye development, the effects of an mi loss of function mutation on RPE and neural retinal were investigated 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 antibodies. Photoreceptor loss was quantified by counting the number of photoreceptor nuclei spanning the outer nuclear layer throughout postnatal retinal development.
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 morphology. The dorsal region of mi/mi retinal pigment epithelium expands and forms an ectopic retina, which develops all major retinal cell types along a similar time course as the wild type. After birth, mi/mi photoreceptors begin to form rosettes, outer segments fail to elongate, and over an extended time 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 RPE to retina in the dorsal eye.
Insights
The microphthalmia (mi) gene is crucial for retinal pigment epithelium (RPE) development and function. Loss of mi function in mice leads to RPE abnormalities and a transformation of dorsal RPE into ectopic retina.
Area of Science:
- Developmental biology
- Genetics
- Ophthalmology
Background:
- Microphthalmia (mi) is a bHLH-zip transcription factor essential for retinal pigment epithelial (RPE) development and pigmentation.
- The RPE layer is critical for optic vesicle and optic cup development.
- Understanding the role of mi is key to deciphering eye development processes.
Purpose of the Study:
- To investigate the role of microphthalmia (mi) in eye development.
- To determine the effects of an mi loss-of-function mutation on RPE and neural retina development in mi/mi mice.
Main Methods:
- Sectioning and antibody labeling of embryonic and postnatal mi/mi and wild-type mouse eyes.
- Using neural retina- and RPE cell type-specific antibodies.
- Quantifying photoreceptor loss by counting nuclei in the outer nuclear layer.
Main Results:
- Early neural retina differentiation proceeds normally in mi/mi mice.
- Ventral RPE in mi/mi mice fails to pigment and achieve cuboidal morphology.
- Dorsal RPE in mi/mi mice expands, forming an ectopic retina with all major retinal cell types.
- Postnatal mi/mi retinas exhibit photoreceptor rosettes, failed outer segment elongation, and degeneration.
Conclusions:
- Normal early retinal development can occur without functional mi.
- Later retinal histogenesis depends on a differentiated RPE.
- Loss of mi function induces a dorsal RPE-to-retina cell fate change.