According to the National Center for Health Statistics, National Health Interview Survey (Disability Supplement, 1994 and 1995), approximately 1.3 million people in the U. S. were legally blind, with estimated annual cost of $4 billion to the federal government. In the developed countries, a majority of diseases leading to untreatable blindness involve the death of photoreceptors. Since photoreceptors are non-dividing neurons, they cannot be replaced after death. As such, maintenance of live photoreceptors and/or their replacement by intervention are active areas of investigation for treatment and therapy of retinal and macular diseases.
Researchers at the University of Michigan have demonstrated successful repair of the retina and restored visual function by transplantation of precursor photoreceptor cells. The team has discovered a transcriptional regulatory factor, NRL, which regulates the expression of many important genes in rod photoreceptors and that this regulatory factor is essential for the generation of rods. In its absence, photoreceptor precursors are converted to cones. Using the NRL regulatory sequences, methods to identify, tag and purify mouse retinal cells that are destined to become rod or cone photoreceptors have been developed. The investigators showed that post-mitotic rod precursors integrated and formed appropriate synaptic connections rather than previously thought stem and progenitor cells. Donor cells isolated at the peak of rod genesis expressing NRL integrate, respond to appropriate light stimuli, and restore visual function. The identification and characterization of rod photoreceptor precursors has numerous therapeutic applications in medicine for transplantation of cells in the degenerating retina, to restore loss of vision resulting from disease, aging, and injury.
Applications and Advantages
- Novel therapeutics for retinal degenerative-nl-diseases
- Evaluation of small molecules for-nl-photoreceptor generation and survival
- Transcriptional factor-based approach