Researcher(s)
- Heather Boliver, Biological Sciences, University of Delaware
Faculty Mentor(s)
- Velia Fowler, Biology, University of Delaware
Abstract
Purpose: Non-muscle myosin IIA (NMIIA) self-associates to form bipolar filaments and pulls on actin filaments (F-actin) to generate contractile force and regulate many cellular processes. NMIIA mutations cause bleeding disorders, and can affect the kidney, hearing, and cause cataracts in humans. One of the most common human NMIIA mutations, E1841K, alters NMIIA bipolar filament assembly. We aim to determine the role of the NMIIA- E1841K mutation in cataract (eye lens opacification) formation, using full-body knock-in genetic mice.
Methods: Lens clarity was evaluated. Whole-mount imaging was performed to determine lenses’ cellular and capsule structures. RNA was extracted from control and mutant lens epithelial peels to measure relative gene expression of EMT and capsule markers.
Results: 50% of the 8-month-old E1841K homozygous mutant mice presented with anterior dot-like opacities or pyramidal cataracts in one or both eyes, while control and heterozygous lenses were transparent. The lens capsule, the extracellular matrix, appeared irregular in the cataractous lens in the mutant mice. In addition, images of the lens epithelial cells in the cataractous region appeared as mesenchymal-like cells. The homozygous mutant mice with cataracts also had significantly higher mesenchymal marker expression, while having significantly lower epithelial marker expression, suggesting epithelial-to-mesenchymal transition (EMT) is occurring. Furthermore, collagen 4 (Col4), a major component of the lens capsule, exhibited altered gene expression in the mutant, indicating that the lens capsule composition is affected in the mutant mice with cataracts.
Conclusion: Overall, our results suggest that the NMIIA-E1841K mutation causes EMT and alters capsule composition, contributing to the cataract formation in the 8-month-old mice.