Scientists Uncover Promising Pathway for AMD Treatment

In Singapore, a group of scientists has uncovered novel characteristics in transplanted stem cell-derived retinal pigment epithelial (RPE) cells, offering potential advancements in the treatment of age-related macular degeneration (AMD), one of the leading causes of irreversible blindness and visual impairment among the elderly.

Through experiments on preclinical models, the research team pinpointed a unique subset of transplanted RPE cells that closely mimic the behavior of healthy adult human RPE cells, crucial for supporting vision.

The research team, led by Dr. Bhav Parikh, a Scientist at A*STAR's IMCB, and Dr. Paul Blakeley, a Senior Research Fellow at NUS Medicine, used single-cell RNA sequencing technology to understand the genetic behavior of individual cells in preclinical models, encompassing aspects such as their survival and maturation.

The results emphasized that post-transplantation, stem cell-derived RPE cells undergo evolution, giving rise to a subpopulation that closely resembles mature human RPE cells. This particular subpopulation expresses genes that are conducive to vision and the sustenance of cell life. This underscores the crucial importance of scrutinizing transplanted retinal cells at the single-cell level to uncover specific cellular changes that influence the outcome and efficacy of retinal cell therapy.

These insights hold the potential to assist researchers in enhancing the survivability, functionality, and integration of transplanted retinal cells within the host, as well as in the development of future therapeutics for eye conditions.

Projections indicate that by 2040, AMD will affect approximately 288 million individuals. While ongoing clinical trials for retinal cell therapy have demonstrated safety, there remains a lack of an approved cell therapy product for AMD. This deficiency can be attributed to the absence of robust methodologies for evaluating the effectiveness of transplanted RPE cells, encompassing their survival and integration into the human eye to facilitate vision recovery.

This study gives novel insights into the biology and functions of transplanted RPE cells, potentially advancing our comprehension of cell-based therapeutic approaches for AMD and other eye-related conditions in the future.

"Advancing AMD treatments via cell therapy hinges on uncovering the key elements that bolster the endurance, integration, and functionality of stem cell derived RPE cells after transplantation into the eye. Using single-cell RNA-sequencing, we discovered the precise factors that empower RPE cells to not only survive but also integrate and perform optimally in supporting vision," said Dr. Parikh, lead author of the study and Scientist at A*STAR's IMCB.

"This work has future implications to enhance outcomes of RPE cell therapy. For example, prior to transplantation, RPE cells in culture that display this distinct gene expression profile can be selectively chosen for RPE transplant to enhance post-transplant survival. Moving forward, we hope to develop manufacturing processes in line with cGMP regulations to culture these 'superior' RPE cells for AMD treatment," said Dr. Su Xinyi, corresponding author of the study, Acting Executive Director at A*STAR's IMCB and Assistant Professor at NUS Medicine.

"Current therapies in AMD based on pharmacological agents have limited effect in cases of advanced visual loss. Cell-based therapy may address this important unmet need. This work is important in advancing cell-based therapy in AMD," said Professor Gemmy Cheung, Head, Medical Retina Dept, Singapore National Eye Centre (SNEC) and Head, Retina Research Group, SERI.

Reference

Bhav Harshad Parikh et al, Single-cell transcriptomics reveals maturation of transplanted stem cell–derived retinal pigment epithelial cells toward native state, Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2214842120