The retinal regeneration research has great potential for offering new areas for the curing of degenerative diseases in the retina. A lot of animal models are utilized in the study of retinal degeneration for years. These studies have provided great insights and valuable information about different aspects of this process. That being said, the mechanisms and procedures that are responsible for this phenomenon are still not fully explainable. A lot of studies have introduced and explained a new model system for retinal regeneration research that makes use of tadpole; the African clawed frog.
Methods Used
The frog under study is also called the XenopusLaevis. The neural retina of Laevis is surgically removed at stages 51-54, after which a heparin-coated bead dipped in a chemical called FGF-2, is put in the eyes to increase the regeneration. Thorough analyses are done that include Histological and DiI tracing to see the regeneration process.
Other than this, there are other similar surgical approaches used as well where concomitant removal of the anterior part of the eye is utilized to evaluate how well the retinal pigmented epithelium (RPE) works. This is done to regenerate the retina. In order to clearly explain the intracellular mechanism used in this proves, the immunohistochemistry is done for FGF receptors. Moreover, a complicated procedure known as the phosphorylated extracellular signal-regulated protein kinase (pERK) is also conducted. Mitogen-activated protein kinase (MAPK) is also considered and it’s role is confirmed via a pharmacological method that makes use of MAPK kinase inhibitor. (Vergara & Rio-Tsonis, 2009)
Introduction
A vast majority of people around the world are affected by retinal degenerative issues. These diseases and illnesses include macular degeneration, diabetic retinopathy, and even glaucoma that further results in eyesight loss or complete blindness. Even in this day and age, when treatments and medical procedures are very sound and are able to determine the disease in the early stages, but when the retina gets damaged severely there is no treatment procedure available to recover the damage. This is why research regarding retinal regeneration is very crucial as it can allow for the development of new therapeutic strategies and plans that can help treat these pathologies and illnesses.
There are certain species of amphibians that are considered the best animal models for these sorts of studies because of their superb regenerative abilities. In the past few years, there has been a lot of progress in understanding and learning the mechanisms of molecules that are responsible for spontaneous retinal regeneration in the amphibians. (Tareh&Pittack, 1996) the retinal pigmented epithelium in this system can regenerate a damaged, injured or lost neural retina with the help of a process known as transdifferentiation. The process of transdifferentiation involves a complex process in which mature cells are proliferated. Further differentiation also occurs for all the various cell types that make the normal tissue. This whole process is easy to understand, as everything is very evident, but the lack of tools in molecular biology to work on the urodele amphibians poses challenges. Moreover, the large and unarranged genome create a lot of challenges when used as animal models. Therefore, other vertebrate model organisms are now brought into use for retinal regeneration research. A fair example of this is the embryonic chick model that has begun offering information and insights into the molecular pathways that are used in retinal regeneration of various cellular sources for the eye. This includes RPE transdifferentiation (Spence, MAdhavan, Aycinena, & Rio-Tsonis, 2007). Even though the model shows clear benefits, chicks are still only able to regenerate the whole retina when a small window of embryonic development opens. Here the neural retina is not completely differentiated. There are other animal models that have been established like the goldfish and zebrafish. In these models, special cells known as the Muller glial cells are shown that have the potential to regenerate the retinal neurons. That being said, this process only happens if the retinal loss is incomplete and the process does not involve RPE transdifferentiation.
Coming to the XenopusLaevis, this is by far the most studied and analyzed anuran amphibian by scientists and researchers. This amphibian has been used for research purposes, especially in the developmental biology field for years. Majority of its genes are identified and a huge variety of molecular biology methods and approaches are set in place for this species. The only drawback is that its potential in retinal regeneration research is still not fully covered, and there are many grey areas. The ability of the XenopusLaevisRPE to transdifferentiate into the neural retina is shown by the transplantation of RPE explants. This is taken from the eyes of tadpoles or the adult frog.
The process of transdifferentiation of RPE into the retina in this process is made possible by several factors offered by the neural retina. This is because the explants transplanted in the center of the enucleated eye along with the ones that are transplanted in the anterior chamber of host species’ eyes could not properly transdifferentiate. There have been multiple studies to find out the factors produced by the mature retina that induces fate decisions in the RPE. These studies have suggested that a good candidate for this kind of molecule is fibroblast growth factor 2 (FGF-2). This is because the incubation of explants when this factor is present can go up to a month. FGF-2 is also a proven induction factor in the RPE transdifferentiation in several other animal models; the embryonic chick is an example of this. However, there is still a dire need for extra mechanisms and procedures to be set in place to avoid the retina from inducing transdifferentiation of the usual adjacent RPE layer.
References
Spence, Madhavan, Aycinena, & Rio-Tsonis, D. (2007). retina regeneration in the embryonic chick is not induced by spontaneous mitf downregulation but requires FGF/FGFR/MEK/ERK-dependent upregulation of Pax6. Mol Vis, 57-65.
TAReh, &Pittack. (1996). transdifferentiation and retinal regeneration. Semin Cell Biol, 137-142.
Vergara, M. N., & Rio-Tsonis, K. D. (2009). Retinal regeneration in the XenopusLaevis Tadpole: a new model system. Molecule Vision Biology and Genetics In Vision Research.
