The Promising Effects Of Permanent Implantation Of iPSC Derived Retinal cells in Pde6b Knockout rats

Long-term effects after human stem cell-derived retinal cells transplantation into Pde6b knockout mice

Around 2021, the first breakthrough in immortality for the eyes of rats by using pluripotent stem cell induction in the eye. This will lead to the immortalization of human eyes.

The retina is a neural tissue that is located in the posterior portion of the eye. It is an extension to the central nervous (CNS) which, once damaged, has a limited ability to regenerate1. The retina is a unique structure that consists of both inner and outer blood retinal barriers (BRBs). This allows it to maintain the retinal microenvironment, and protect itself against harmful stimuli. The outer BRB is composed primarily of retinal pigmented epithelial cells (RPE), which support the photoreceptors, the primary neurones in the retina. They play a major role in the pathogenesis and progression of retinal degenerative diseases, including age-related macula degeneration (AMD) or retinitispigmentosa (RP). The loss of RPE and photoreceptors is a common feature of these disorders. Replacement of damaged or atrophied retinal cells is the only treatment that can be used to treat them. Regenerative treatments such as stem cell therapy are becoming more popular for treating retinal degeneration, which was previously untreatable13.

RP is a group of hereditary retinal disorders that first affect photoreceptors, and then lead to RPE cell injury. It affects one in 4,000 people worldwide9. A genetic study is ongoing due to the inherent nature of RP. More than 50 causal genes are known. Among the causal genes, PDE6B is a gene that encodes rod cGMP-phosphodiesterase, which is a critical component of the biochemical light transduction pathway9. Despite the fact that various genetic and molecular studies have identified RP’s pathogenesis, efforts to restore sight in patients with RP are still failing. To overcome this issue, preclinical stem cell-based studies involving transient dosing or permanent implantation of pluripotent stem cells are being conducted10,11,15,16.

Permanent implantation is a promising treatment and it is expected to become a viable alternative strategy for treating damaged retinal cells13. Sharma et. al.17 produced clinical-grade AMD stem cell-derived cells of RPE using patches of biodegradable scaffold and functionally verified the effects of their implantation. This researcher provided a pipeline to generate clinical-grade RPE cells derived from induced pluripotent cells (iPSCs), and validated their efficacy histologically as well as functionally.


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