Purchase this article with an account.
Anthony Sallese, George Tsissios, Vayda Barker, Abby Crothers, Alyssa Miller, Panagiotis Tsonis, Katia Del Rio-Tsonis; Regulating lens regenerative potential through Eph receptor signaling. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3304.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
The newt iris is comprised of pigmented epithelial cells (iPECs) but only those located at the dorsal iris can undergo transdifferentiation in order to regenerate a new lens. Recent transcriptomic and proteomic analysis compared dorsal and ventral newt iPECs and identified several regulated genes during the process of lens regeneration, including Eph/ephrin family members. Based on those studies, we hypothesize that an Eph/Ephrin signaling network restricts lens regeneration to the dorsal iPECs.
Adult Notophthalmus viridescens, red spotted newts, were treated at day (D)0, D2, and D4 post-lentectomy, with FC chimera proteins to inhibit Ephrin receptors (EphB2, EphA4, EphA5) and ligands (EphrinB2 and EphrinA5). Thirty days post-lentectomy, histological and immunohistochemical analysis were performed. In addition, surgically separated dorsal and ventral iris halves were treated in vitro and analyzed as described above.
Ventral lens regeneration was induced, in vivo, with EphA4 and EphA5 inhibition. In the majority of cases, both a dorsal and ventral lens were present. EphB2, EphrinB2, and EphrinA5 inhibition did not induce a ventral lens. Similar results were observed in vitro using separated dorsal and ventral iris segments.
This is the 1st report of ventral lens regeneration in vivo with a known treatment. We show that inhibition of Eph receptor signaling induces ventral lens regeneration in vitro and in vivo. Eph/Ephrin signaling is best known for regulation of cell migration and border formation. However, in vitro studies identified ventral iPECS were still able to undergo lens regeneration in the absence of dorsal iPECs. These results suggest migration of regeneration competent dorsal cells into the ventral region is not a primary driver of the observed lens regeneration. We propose Eph receptor signaling in the ventral iris is inhibiting signaling pathways central for the induction of lens regeneration. Future studies will focus on identifying these downstream signaling targets.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
This PDF is available to Subscribers Only