Human health is compromised with age, disease, and trauma. In the eye, these events lead to reduced visual acuity and blindness. It is expected that the occurrence of eye diseases like age-related macular degeneration, diabetic retinopathy, and glaucoma, would double by 2050, further emphasizing the need for restorative treatments1. Newts are known to regenerate most of their body parts, including eye tissues2–4. However, it wasn’t until recently that scientists had the capacity to utilize modern molecular and genetic methodologies to explore the biology behind salamander regeneration5. My research lab is taking advantage of technologies such as CRISPR, transgenesis, and single cell sequencing to understand eye tissue regeneration in newts. Unraveling the mechanism that allows newts to replace damaged eye tissues could inform future regenerative treatments for human patients with eye diseases.
The impressive regenerative capacity of the newt eye stems from its pigmented epithelium; a thin sheet of melanin-bearing cells that surround the retina and extend towards the pupil. Following injury, retina pigmented epithelial cells regenerate the retina while iris pigmented epithelial cells (IPECs) regenerate the lens6,7. Newt lens regeneration by IPECs is a very attractive model to study vertebrate eye restoration due to its unique technical advantages. These include: (1) the simple cellular composition of the iris which reduces experimental background, (2) the well-defined cellular origin of lens regeneration as IPECs, (3) the short, two-week regeneration timeline, (4) the presence of an internal negative control where only dorsal-residing IPECs participate during lens regeneration while ventral-residing IPECs do not, and (5) the presence of a non-newt salamander, the axolotl, that cannot regenerate their lens and can be used for cross-species comparative studies8. Axolotls allow for proof-of-concept translational studies in a non-regenerative environment before tests can be conducted in higher vertebrates. This greatly reduces the risk of this project, which I believe is critical to successfully induce a salamander-like regenerative event in mammals in the future.
