The lens capsule is an acellular, thickened basement membrane that completely surrounds the lens from its earliest developmental stages until death. Numerous studies have shown that the capsule is essential for lens development and function and a number of human and animal diseases result in lens capsule abnormalities, often leading to the degradation or destruction of vision. Recently, we demonstrated that the composition of the collagen IV network changes during lens development so that the collagen IV subtypes associated with basement membrane elasticity are expressed during early development while those associated with basement membrane strength are not expressed until after eye lid opening. This led to the hypothesis that the expression of lens capsule components changes during development to allow for both the 200 fold increase in capsule area during embryogenesis and the strength necessary for accomodation. This hypothesis will be tested by changing the collagen IV subtype composition of the lens using transgenic mouse approaches. Since at least one class of basement membrane molecules is differentially synthesized during lens development, we hypothesize that other basement membrane molecules will have similar expression profiles which could also have dramatic consequences on lens function. Thus, the developmental expression pattern of extracellular matrix molecules found to be expressed in the lens by our prior microarray analyses will be determined as well. The role that both the changing collagen IV subtype composition and the presence of other extracellular matrix molecules in the lens capsule plays in lens biology will be tested by cell adhesion, migration and proliferation assays on either primary cultures of mouse lens epithelial cells or freshly isolated bovine lens epithelial cells in the presence or absence of matrix components. These studies will both elucidate the molecular composition of the lens capsule and address the role that the capsule plays in the biology of the attached lens cells.
| Wang, Yichen; Mahesh, Priyha; Wang, Yan et al. (2018) Spatiotemporal dynamics of canonical Wnt signaling during embryonic eye development and posterior capsular opacification (PCO). Exp Eye Res 175:148-158 |
| Audette, Dylan S; Scheiblin, David A; Duncan, Melinda K (2017) The molecular mechanisms underlying lens fiber elongation. Exp Eye Res 156:41-49 |
| Wang, Yichen; Terrell, Anne M; Riggio, Brittany A et al. (2017) ?1-Integrin Deletion From the Lens Activates Cellular Stress Responses Leading to Apoptosis and Fibrosis. Invest Ophthalmol Vis Sci 58:3896-3922 |
| Sadaka, Ama; Sisk, Robert A; Osher, James M et al. (2016) Intravitreal methotrexate infusion for proliferative vitreoretinopathy. Clin Ophthalmol 10:1811-1817 |
| Lyu, Lei; Whitcomb, Elizabeth A; Jiang, Shuhong et al. (2016) Unfolded-protein response-associated stabilization of p27(Cdkn1b) interferes with lens fiber cell denucleation, leading to cataract. FASEB J 30:1087-95 |
| Pathania, Mallika; Wang, Yan; Simirskii, Vladimir N et al. (2016) ?1-integrin controls cell fate specification in early lens development. Differentiation 92:133-147 |
| Mamuya, Fahmy A; Wang, Yan; Roop, Victoria H et al. (2014) The roles of ?V integrins in lens EMT and posterior capsular opacification. J Cell Mol Med 18:656-70 |
| Pathania, Mallika; Semina, Elena V; Duncan, Melinda K (2014) Lens extrusion from Laminin alpha 1 mutant zebrafish. ScientificWorldJournal 2014:524929 |
| Scheiblin, David A; Gao, Junyuan; Caplan, Jeffrey L et al. (2014) Beta-1 integrin is important for the structural maintenance and homeostasis of differentiating fiber cells. Int J Biochem Cell Biol 50:132-45 |
| Simirskii, V N; Duncan, M K; Paltsev, M A et al. (2013) ?1 integrin as the integrating component in cell-cell cooperation for maintenance of lens transparency. Dokl Biochem Biophys 453:297-9 |
Showing the most recent 10 out of 27 publications
