Abstract
Purpose :
Salamanders have the capacity to regenerate a fully functional lens as adults via the reprogramming of iris pigment epithelial cells. Interestingly, this ability is restricted to the dorsal and not the ventral iris. We have focused on dissecting gene regulation that dictates this regenerative competence.
Methods :
We performed RNAseq and spatial transcriptomics to delineate regional patterns in gene expression across the irises of two newt species, the Eastern newt (Notophthalmus viridescens) and Iberian Ribbed newt (Pleurodeles waltl). Pathways identified via RNAseq were disrupted via injection of molecular inhibitors into the vitreous cavity following lentectomy, and the effect on regenerative outcome was assessed via optical coherence tomography and histology.
Results :
Our data points towards a highly conserved patterning axis associated with vertebrate eye development that is maintained across the newt iris into adulthood. Interestingly, our data suggests that this network directs regenerative competence in newts. Upon injury (lens removal), a gene program orchestrated by BMP modulators assures that lens regeneration is restricted to the dorsal iris. In parallel, Ephrin signaling is essential to maintain iris polarity, and disruption of this pathway is sufficient to induce ventral iris pigment epithelial cells to regenerate a lens in vivo.
Conclusions :
Our results demonstrate that a highly-conserved patterning axis that governs vertebrate eye development is present in the adult newt eye, and which appears to have been co-opted to modulate regenerative competence within the newt iris.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.