Shu-Zhen Wang, PhD
Dept. of Ophthalmology
Chinese Academy of Agricultural Sciences, Beijing, China
MS, Plant Genetics, 1981
Virginia Polytechnic Institute and State University, Blacksburg, VA
PhD, Molecular Genetics, 1985
Photoreceptors are a group of specialized sensory cells in the vertebrate neural retina. Their degenerations are a common cause of human visual impairments resulting from light damage, the aging process, or from genetic defects, including age-related macular degeneration-the leading cause of irreversible severe vision loss in the elderly in the United States. The low quality of life of individuals with severe vision loss has stimulated investigations ranging from photoreceptor rescue to photoreceptor replacement. The unfortunate non-renewable nature of photoreceptor cells has limited experimentation of photoreceptor cell replacement to the use of embryonic retinal cells or an electronic device. However, replacement with a pure population of regenerated photoreceptor cells is likely to be superior to that with a mixture of many cell types or with a physical device.
Recent studies from this laboratory have shown that forced expression of NeuroD can induce retinal pigment epithelium (RPE) cells derived from day 6 chick embryos (E6) to transdifferentiate into photoreceptor cells selectively. This raises an exciting possibility of exploring RPE plasticity and NeuroD, as a molecular trigger, to regenerate photoreceptor cells. However, further investigations are needed before testing this possibility in animal models for certain forms of human blindness.
First, we need to know who are the molecular triggers and who are the enhancers. This means that we need to identify and understand the model of action of genes that are important for selection of photoreceptor cell fate and subsequent establishment of cell property. Second, we need to RPE cells along a desirable pathway, so that to produce photoreceptor cells selectively, through employing those molecular triggers and enhancers. In addition to the study of the molecular mechanism underlying retina cell fate determination and cellular differentiation, and the molecular events unfolding during RPE transdifferentiation, we will also ask whether those regenerated cells can establish connectivity or conductivity with the rest of the retina. These are some example questions we wish to study in the future.
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