1334-P: Hyperglycemia-Induced Eye Malformations through Dysregulation of Autophagy in the Mouse Embryo

Abstract

Accumulating evidence indicates that autophagy is essential for development and its dysregulation is involved in maternal diabetes-induced fetal malformations. Maternal diabetes induces fetal eye defects by reducing macular thickness and macular volume. We utilized the Streptozotocin-induced type 1 diabetes model to investigate the role of autophagy in maternal diabetes-induced embryonic eye defects. We found that maternal diabetes induced eye defects in the embryonic day (E15) embryos including anophthalmia, microphthalmia. The Haematoxylin Eosin staining showed some severe defects: coloboma, smaller lens, and smaller volume of eyes. In some cases, there were failures to fully develop eye structures. In these embryonic eye defects, the thickness of retinal was significantly thinner than that in the nondiabetic group. Our hypothesis is that maternal diabetes induces embryonic eye malformations by suppressing autophagy. Maternal diabetes increased cell apoptosis and suppressed cell proliferation in retinal of the eye. We found that autophagy-related genes (ATGs) was robustly expressed in the lens and retina of the eyes of mouse embryos and was suppressed by maternal diabetes. Maternal diabetes suppressed the expression of pax6, a key gene in visual system development. Taken together, our data demonstrates that autophagy is important for eye development and maternal diabetes induces embryonic eye defects by inhibiting autophagy. Disclosure W. Lu: None. P. Yang: None. Funding National Institutes of Health (R01DK083243, R01DK101972, R01HL131737, R01HL134368, R01DK103024)