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Raju Rajala

Application of Lipid Nanoparticles for Retinal Degenerative Diseases. The application of viruses as a carrier to deliver genes to eye tissue was successful, although unsafe. We have created an artificial virus using a nanoparticle, liposome-protamine-DNA complex (LPD), modified with a cell-permeable peptide and a nuclear localization signaling (NLS) peptide, to deliver a functional gene for the treatment of eye disease. We showed for the first time that LPD promotes efficient delivery in a cell-specific manner, and long-term expression of the Rpe65 gene to mice lacking Rpe65 protein, leading to in vivo correction of blindness. Thus, LPD nanoparticles could provide a promising, efficient, non-viral method of gene delivery with clinical applications in eye disease treatment that apply to other tissues. In addition, we successfully applied LPD to deliver miRNA-184 to repress Wnt-mediated ischemia-induced retinal neovascularization (oxygen-induced retinopathy). Currently, we are using these particles to deliver miRNA, lipids, drugs, and genes to retinas that are predetermined to degenerate to delay or halt the degeneration.

3D Bioprinting of the Retina. In biology, regeneration is the process of renewal, restoration, and growth that makes genomes, cells, organisms, and ecosystems resilient to natural fluctuations or events that cause disturbance or damage. Every species, from bacteria to humans, is capable of regeneration. Unfortunately, the photoreceptor neurons in the retina do not regenerate once they reach maturity. Keeping these photoreceptor neurons in a healthy state is a challenging task for humans. These cells are important in the retina as they absorb light and convert the signal to the neurological impulse, which aids in visual perception. Vision loss affects millions of people each year due to various environmental and genetic factors. This results in the complete loss of vision because of the death of photoreceptors, also known as degeneration. Recent advances in gene therapy rescued vision from further degeneration by replacing defective or lost genes. Unfortunately, by the time the symptoms of degeneration appear, many photoreceptors have already been lost. We hope that one day we will make these photoreceptors in a test tube and transplant them to the retina that is undergoing retinal degeneration. Studies are underway in our laboratory to print these cells outside the body and study their behavior; ultimately, these cells would be used to replace the dying photoreceptors. If successful, the significance of this research is potentially high as it not only benefits blinding disorders, but also should have broad applicability to other neurological diseases.