Giving Patients Hope: Regeneration and Restoration
Growing back the optic nerve
Dr. Toru Nakazawa introduced the steps for regenerative medicine based on retinal ganglion cell transplantation. He gave some details about what we need for regenerative medicine to restore visual functions.
Stem-cell therapy is being widely explored as a treatment for degenerative eye diseases. He showed that we have basic two types of treatment for stem-cell: direct and indirect treatment.
In conclusion, he finished saying that regenerative medicine based on RGC transplantation calls for research into many steps of the process, including the cell source, transplantation, axonal growth, scarring, synaptogenesis, and topography. At this moment, there is rapid progress at the level of basic research.
Tissue engineering for the anterior segment
Dr. Nils Loewen divided his lecture in four sections: restoring outflow with drugs, trabecular cytoablation + repopulation, prostaglandin gene therapy and towards chronic distal outflow tract dilation.
First, he gave some details about the outflow pathway in young and elderly human. He also explained about the uveal and conventional outflow and the specific drugs that impact these outflows. He emphasized some side effects of these drugs specially in the eyelid’s areas.
Second, he presented some aspects of laser trabeculoplasty and aspects about TM repopulation of TM matrices.
Third, he explained the prostaglandin gene therapy flow and last he summarized the chronic distal outflow tract dilation (delivering dilating transgenes).
Turning stem cells into retinal ganglion cells: A translational model of neurodegeneration and human disease pathology
Prof. Jason Meyer introduced the definition of glaucoma, how they affect retinal ganglion cells and how visual field will be after the development of the disease. He introduced the neurodegeneration model in experimental studies.
In his lab hPSC-RGCs provided a simplified in vitro model of human RGCs trying to find application for retinal development or disease modeling. And in the future for drug development or cell replacement.
As we know, there are multiple risk factors for glaucoma. For example, CIRSPR/Cas9 gene was edited to create appropriate models of disease. They followed the cells over time and they found the differentiation of the cells.
In conclusion, they found that RGCs can be differentiated from hPSCs; hPSC-RGCs can provide insight into human-specific phenotypes; neurodegenerative phenotypes can be examined in hPSC-RGCs and can serve as a plataform for therapeutic development and lastly, co-cultures of RGCs and astrocytes can be used to examine non-cell autonomous aspects of the disease state.
Gene therapy for optic nerve repair
Dr. Keith Martin explained one possible use of gene therapy in future. He gave some historic marks about the use of neuroprotective gene in Leber’s congenital amaurosis, later in Leber’s hereditary optic neuropathy and also in choroideremia.
They are working hard developing a combined TrkB-BDNF gene therapy as a neuroprotector gene. They demonstrated in experimental studies that may keep the function of RGCs.
He gave some thoughts about other future treatments for glaucoma and how gene therapy can act. CNS axons have a poor intrinsic regenerative ability to regenerate. So, they are working on integrins that are cell surface receptors for the extracellular matrix. They are very important for regeneration. One molecular that they are also interested and that they are studying are protrudin. This molecular is also associated with the capability of regeneration.
In summary, gene therapy is a realistic approach for many eye diseases including glaucoma and clinical trials of neuroprotection and neuroenhancement are feasible. Finally, gene therapy also promising for optic nerve degeneration and cell reprogramming.