Table 2 Future directions for transplantation methods and models (SDG2)
Research Area | Future Goals |
|---|---|
Anatomically accurate models | Evaluate RGC transplantation in models that accurately mimic the human eye’s anatomical features, including the macula and the collagenous lamina cribrosa, to study neuronal transplantation in various pathological contexts |
Disease models | Establish models for studying neuronal transplantation in different pathological contexts such as normal aging, normal-tension glaucoma, autoimmune disease, and developmental models that do not induce active neurodegeneration |
Larger animal models | Prioritize larger animal models to develop clinically relevant transplantation techniques, including procedures like pars plana vitrectomy, internal limiting membrane (ILM) peeling, and implantation of rigid scaffolds |
First-in-human trials | Define an “ideal” optic neuropathy patient suitable for initial clinical trials and establish an experimental model to mirror this clinical phenotype |
Transplantation timing | Investigate the effect of disease progression and aging on the survival and integration of donor cells |
Overcoming barriers to engraftment | Evaluate use of immunomodulatory agents and extracellular matrix modulators to promote cell survival and integration |
Graft specifications | Investigate the effects of different cell doses on graft survival, integration, and functional outcomes. Explore the potential benefits and optimal ratios of transplanting a mixture of RGCs and non-RGC support cells |
Immune responses | Explore methods for promoting immunotolerance of transplanted RGCs, such as immunosuppressive drugs, gene editing techniques, or extracellular matrix modulators that may improve cell survival and integration by inhibiting reactive gliosis and immune cell infiltration |
Scaffolds | Explore new techniques for delivering donor RGCs to the retina, such as developing improved scaffolds or designing methods that allow for safe and efficient migration of donor cells from the epiretinal surface |
Delivery methods | Evaluate and develop alternative cell delivery methods, such as sub-ILM transplantation, which may offer better donor cell survival and integration outcomes |
Preconditioning techniques | Investigate diverse preconditioning methods to improve donor cell resistance to hypoxia, para-inflammation dysregulation, and oxidative stress |
Quality control and validation | Implement quality control measures throughout the transplantation process and validate results using multiple complementary and standardized methods to facilitate accurate characterization and labeling of transplanted cells, including the possibility of material transfer |
Imaging capabilities | Improve imaging for experimental and translational purposes, benchmarked to OCT metrics as the primary structural outcome in human patients |