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  • April 20, 2020
  • Author: EURETINA Brief

Reprogramming of fibroblast cells into photoreceptor cells restore vision, without the need of stem-cells or viral treatment.

A significant research report, published in the journal Nature, has demonstrated that fibroblast cells could be reprogrammed into rod photoreceptor-like cells allowing the reversal of vision loss.  The research team, based at the University of North Texas Health Science Centre and the National Eye Institute, National Institutes of Health, Bethesda, has used a set of five small molecules to chemically induce the transformation of the retinal cells, providing partial restoration of the pupil reflex and visual function.  The research was conducted in an experimental model for retinal degeneration and the team is now focused on preparing clinical research studies.  Commenting on the work at the NEI, Dr. Anand Swaroop stated: “This is the first study to show that direct, chemical reprogramming can produce retinal-like cells, which gives us a new and faster strategy for developing therapies for age-related macular degeneration and other retinal disorders caused by the loss of photoreceptors.”

 

Previously, stem-cell therapy using either embryonic stem cells, or induced adult pluripotent stem cells (iPS), may have required up to 6 months to derive candidate replacement cells.  However, using the new protocol, the current technique may reprogramme photoreceptor-like cells within 10-days.  This approach uses a set of five small molecules to induce fibroblast cells preparing functional “CiPCs” – chemically induced photoreceptor-like cells.  These molecules include valproic acid (V), CHIR99021 (a GSK3 inhibitor) (C), RepSox (R) and forskolin (F), together denoted VCRF, and a final inhibitor, IWR1.  These five compounds in combination were able to convert fibroblasts into CiPCs without the need for pluripotent cells or viral transcription factors. The CiPCs demonstrated a transcriptome that resembled the characteristics of native rod-photoreceptor cells and, when transplanted CiPSs into the subretinal space in rd1 models, 43% of the study cohort provided an improved pupil response.

 

Commenting in the paper in the Nature report, the researchers concluded that: “Although CiPCs have therapeutic potential, a lack of proliferation—as is the case for native photoreceptors—and low conversion efficiency are the main impediments for a translational application. We anticipate that optimization of our current protocol may be beneficial for obtaining large numbers of CiPCs. Overall, CiPCs are a promising cell-replacement candidate and may lead to a scalable therapy for vision restoration.”

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