Eye tissues such as the lens and the retina possess remarkable regenerative abilities in some animals. Our lab concentrates research efforts in the understanding of cellular and molecular events that take place during eye tissue regeneration. Several animal models are used in the lab including the embryonic chick and amphibians such as newts and axolotls. Over the years, we have utilized novel technology and developed innovate tools in order to unravel the molecular mechanisms that orchestrate events during regeneration.
Retina regeneration takes place in a variety of organisms including teleost fish, birds and amphibians. Our lab uses the embryonic chick and amphibians to study mechanisms of retina regeneration.
The chick can regenerate the entire retina during a short window of its development. Upon retina removal, the retinal pigment epithelium (RPE) located behind the neural retina undergoes reprogramming. In this process the RPE dedifferentiates, losing its characteristics of origin and creating a neuroepithelium that can later differentiate into the cells that comprise the neural retina including photoreceptor, amacrine, bipolar, horizontal, ganglion cells and Mueller glia cells. The retina can also regenerate via the activation of stem/progenitor cells located in the anterior margin of the eye.
Newts on the other hand, can regenerate their retina mostly via RPE reprogramming at any time of their life span. Other amphibian models such as axolotls are also been explored in the lab and their regenerative ability is being assessed.
We are interested to determine which signaling pathways and epigenetic programs are key regulators in the process of regeneration, so that one day we could try to induce this ability in higher vertebrates including humans. This could be very beneficial in the cure/treatment of so many of the retinal degenerative diseases.
Tsonis and Del Rio-Tsonis. Exp Eye Res 78(2):161-72, 2004
Luz-Madrigal et al. BMC Biology 12:28, 2014
Several vertebrates have the ability to regenerate but newts are the only animals with the ability to regenerate lens throughout their entire adult lives. Regeneration of the newt lens occurs by transdifferentiation of the pigment epithelial cells (PECs) at the tip of the dorsal iris. These cells dedifferentiate to form a vesicle, which in turn differentiates to form the lost lens.
We would like to know what the switches are that turn on the cell cycle of these cells, as well as the molecules involved in the unique process of dedifferentiation, where cells loose their characteristic of origin and become "embryonic-like". Another approach is to determine if the ventral iris has a negative regulator that inhibits the process all together. Pinpointing these molecular switches could provide the tools to reprogram higher vertebrate cells and eventually induce regeneration. The ultimate goal is to use the obtained knowledge to aid in the understanding and cure of human eye diseases such as cataracts.