In Spain, Researchers Regenerate Retina in Mice: the Laboratory Results

Retinal photo. Credit: Cell Reports Journal

Recently, I learned about a fascinating study in which researchers from the Center for Genomic Regulation (CRG) in Barcelona, Spain have identified a pathway that triggers the reprogramming and regeneration of retinal neurons in the eye; in addition, they have regenerated mouse retinal tissue through cell reprogramming

This research is in its earliest stages and has been conducted only with laboratory mice. Nevertheless, the concept shows great promise for persons with retinal disease.

The study, entitled Wnt/Beta-Catenin Signaling Triggers Neuron Reprogramming and Regeneration in the Mouse Retina, was published in the July 11, 2013 issue of Cell Reports, an international, peer-reviewed, open-access online journal, published by Cell Press. The focus of Cell Reports is cutting-edge research that produces new biological insights.

The authors are Daniela Sanges; Neus Romo; Giacoma Simonte; Umberto Di Vicino; Ariadna Diaz Tahoces; Eduardo Fernández; and Maria Pia Cosma, who represent the following institutions: Center for Genomic Regulation; Institució Catalana de Recerca i Estudis Avançats; Bioengineering Institute, University Miguel Hernández; and the Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine.

About WNT Signaling and Beta-Catenin

Wnt signaling pathways are a group of “transmitters,” composed of proteins, that pass signals from outside a cell to the inside of the cell. Wnt signaling was first identified for its role in carcinogenesis, which is the process by which normal cells are transformed into cancer cells. It also plays a role in embryonic development.

Beta-catenin (or ß-catenin) is one component of a group of proteins that facilitate Wnt signal transmission, regulate cell growth, and enable cells to communicate and adhere – or fuse – to one another. The combination of these elements is referred to as the Wnt/ß-catenin signaling pathway.

Abnormal Wnt signaling can lead to a variety of diseases and disorders, including cancer, type 2 diabetes, brain tumors, and osteoarthritis. Here is more information from Genetics Home Reference at the National Institutes of Health:

Wnt signaling is known to be involved in many aspects of embryonic development. The Wnt signaling pathway controls the activity of genes needed at specific times during development, and it regulates the interactions between cells as organs and tissues are forming.

Mutations that disrupt the functions of Wnt genes during embryonic development have been found to cause birth defects. In adult tissues, Wnt signaling plays a role in the maintenance and renewal of stem cells, which are cells that help repair tissue damage and can give rise to other types of cells.

About the Research

A summary from Science Daily:

Researchers from the Center for Genomic Regulation have managed to regenerate the retina in mice using neuronal reprogramming. There are currently several lines of research that explore the possibility of tissue regeneration through cell reprogramming. One of the mechanisms being studied is reprogramming through cell fusion.

The [research team] has used the cell fusion mechanism to reprogram the neurons in the retina. This mechanism consists of introducing bone marrow stem cells into the damaged retina. The new undifferentiated cells fuse with the retinal neurons and these acquire the ability to regenerate the tissue.

“For the first time we have managed to regenerate the retina and reprogram its neurons through in vivo [i.e., within a living organism] cell fusion. We have identified a signaling pathway that, once activated, allows the neurons to be reprogrammed through their fusion with bone marrow cells,” explains Pia Cosma, head of the Reprogramming and Regeneration group at the Center for Genomic Regulation.

The study … demonstrates that the regeneration of nervous tissue by means of cell fusion is possible in mammals and describes this new technique as a potential mechanism for the regeneration of more complex nervous tissue. This research is in the very early stages but already there are laboratories interested in being able to continue the work and take it to a more applied level.

More about the Study and Results from Cell Reports

From the study Summary and Discussion:

  • Here, we have demonstrated that the … Wnt/ß-catenin signaling pathway [facilitates] the reprogramming of retinal neurons in vivo [i.e., within a living organism].
  • In addition, we have shown that spontaneous cell fusion can occur in the mouse retina after injury and that a proportion of [these newly fused cells reproduce rapidly] if they are reprogrammed by Wnt activity.
  • Furthermore, we have also shown that if the [newly fused cells] are not reprogrammed, they undergo [cell death].
  • Surprisingly, the reprogrammed [fused cells] can regenerate the damaged retinal tissue, although the regenerated tissue is not always [uniform in structure].
  • Finally, we have shown that after … activation of the Wnt signaling pathway in the eye, [bone marrow]-derived cells that are [introduced] into the injured retina can fuse and reprogram the retinal neurons.
  • Here, we have shown that, at least in a mouse retina, regeneration can occur through cell-fusion-mediated reprogramming.
  • On the other hand, there is [non-uniform] regeneration of the transplanted retinas, which indicates that other factors might be used to enhance these processes (e.g., nerve growth factors).
  • …We cannot exclude that in addition to the generation of new neurons … we might have also induced delayed neuronal degeneration.
  • In conclusion, after Wnt signaling activation, retinal neurons can be reprogrammed after cell fusion with [bone marrow cells] and these [newly fused cells] can contribute to cell regeneration and repair of retinal tissue.

VisionAware will provide updates of this innovative research as it moves from the laboratory into human subject testing.

“Schematic representation of retinal tissue” image from Cell Reports under a Creative Commons Attribution-NonCommercial-No Derivative Works license.