Have you ever heard that certain cells in the eye, once damaged, cannot be naturally repaired? This is the predicament faced by many eye disease patients, especially those with retinal degenerative diseases[1]. These diseases, such as age-related macular degeneration (AMD), retinitis pigmentosa (RP), and Stargardt's disease (STGD), lead to irreversible loss of photoreceptor cells in the retina. These cells are responsible for converting light into signals that the brain can interpret as vision, which is crucial for visual function. Once these cells are lost, they do not regenerate naturally, leading to permanent vision impairment or even blindness.

However, scientists have been working tirelessly to find solutions[2], and now they have made a new progress. Scientists have been using a special type of stem cell—chemically induced pluripotent stem cells (CiPSCs)—to successfully cultivate "retinal organoids (ROs)" that mimic the real retina[3]. These organoids not only helped mice with retinal diseases regain their sight but also brought new hope for the treatment of human retinal degenerative diseases. They have discovered that a new method of cultivating stem cells can help repair damaged retinas and may even help people regain their sight [3].

This new method uses CiPSCs, which are safer than traditional stem cells because they are cultivated through special chemical compounds rather than viruses. This means they do not disrupt our genome, reducing safety risks.

Researchers first used these CiPSCs to cultivate structures known as ROs. These ROs are like miniature retinas, containing all important types of retinal cells, including photoreceptor cells that are crucial for capturing light and initiating the visual process. These organoids have gene expression patterns similar to those of the retina in our eyes.

Next, scientists transplanted suspension retinal cells, mostly photoreceptors, from these ROs into the retinas of rd10 mice with retinal degeneration. Excitingly, these transplanted cells not only successfully integrated into the host retina but also established synaptic connections and significantly improved the visual function of the mice.

This research brings new hope for the treatment of retinal diseases. Although the current research is still conducted on mice, its success provides possibilities for future treatment of human eye diseases. Scientists will continue to study how to improve the survival rate and integration of transplanted cells and eventually conduct clinical trials to ensure that this method is both safe and effective for humans. This groundbreaking research not only brings light to mice but also provides a new direction for the treatment of human eye diseases. As research progresses, we look forward to a day when this method can help those who have lost their sight due to retinal degenerative diseases to see again.

References

1. Jin ZB, Gao ML, Deng WL, Wu KC, Sugita S, Mandai M, Takahashi M. Stemming retinal regeneration with pluripotent stem cells. Prog Retin Eye Res. 2019 Mar; 69: 38-56.
2. MacLaren RE, Pearson RA, MacNeil A, Douglas RH, Salt TE, Akimoto M, Swaroop A, Sowden JC, Ali RR. Retinal repair by transplantation of photoreceptor precursors. Nature. 2006 Nov 9;444(7116):203-7.
3. Eiraku M, Takata N, Ishibashi H, Kawada M, Sakakura E, Okuda S, Sekiguchi K, Adachi T, Sasai Y. Self-organizing optic-cup morphogenesis in three-dimensional culture. Nature. 2011 Apr 7;472(7341):51-6.
4. Assawachananont J, Mandai M, Okamoto S, Yamada C, Eiraku M, Yonemura S, Sasai Y, Takahashi M. Transplantation of embryonic and induced pluripotent stem cell-derived 3D retinal sheets into retinal degenerative mice. Stem Cell Rep. 2014 Apr 24;2(5):662-74.
5. Zhao N, Zhang CJ, Zhang X, Wang W, Jin K, Jin ZB. Transplantation of derivative retinal organoids from chemically induced pluripotent stem cells restored visual function. npj Regen Med. 2024 Dec 27;9(1):42.