Eye Lens

 

lens_ifAnatomy + Single Fiber Cell + EM

 

 

 

 

 

 

 

 

 

The ocular lens is a transparent organ in the front of the eye that is responsible for the fine focusing of light onto the retina in order to transmit a clear image. Age-related changes in the lens can cause cataracts, defined as any opacity in the lens, and presbyopia, an inability of the lens to change shape (accommodate) and focus on near objects. Despite decades of study, cataracts remain the leading cause of blindness in the world, and everyone eventually will need reading glasses due in part to stiffening of the lens with age. The exact mechanisms for age-related cataracts and presbyopia remain unclear.

Our work aims to reveal the links between cytoskeletal structures, complex lens cell morphology, lens transparency and overall tissue biomechanical properties. We are interested in understanding the molecular, cellular and tissue level changes that occur with age and/or due to genetic perturbations of actin filament (F-actin) binding proteins. Our work has demonstrated that tropomodulin 1 (Tmod1) and tropomyosins (TMs) play diverse roles in controlling lens cell morphology and hexagonal packing, with distinct effects on lens mechanical stiffness and resilience. For this work, we have perfected a method to easily and reliably measure mouse lens stiffness and developed a novel protocol to isolate lens cells and preserve their complex 3D morphology. By utilizing a wide range of techniques, including high-resolution confocal fluorescence microscopy electron microscopy and proteomics, we can define interactions and structural relationships between F-actin, membrane domains and cell morphologies. This, together with whole lens optical, electrophysiological, and biomechanical experiments, will enable us to understand how F-actin and membrane domain dysfunction leads to cataracts and presbyopia.

 

 

 

 

 

Relevant Publications:

Cheng C, Nowak RB, Biswas SK, Lo WK, FitzGerald PG, Fowler VMTropomodulin 1 regulation of actin is required for the formation of large paddle protrusions between mature lens fiber cells. Invest Ophthalmol Vis Sci. 2016 Aug 1;57(10):4084-4099.

Cheng C, Gokhin DS, Nowak RB, Fowler VM. Sequential application of glass coverslips to assess the compressive stiffness of the mouse lens: strain and morphometric analyses. J Vis Exp. 2016 May 3;(111).

Cheng C, Nowak RB, Fowler VM. The lens actin filament cytoskeleton: diverse structures for complex functions. Exp Eye Res. 2016 Mar 10. pii: S0014-4835(16)30035-5. doi: 10.1016/j.exer.2016.03.005.

Cheng C, Nowak RB, Gao J, Sun X, Biswas SK, Lo WK, Mathias RT, Fowler VMLens ion homeostasis relies on the assembly and/or stability of large connexin 46 gap junction plaques on the broad sides of differentiating fiber cells.  Am J Physiol Cell Physiol. 2015 May 15;308(10):C835-C847.