Steven Bassnett, Ph.D.

Professor
Ophthalmology and Visual Sciences
Cell Biology and Physiology

Molecular Cell Biology Program
Developmental, Regenerative and Stem Cell Biology Program

  • 314-362-1604

  • 314-362-2699

  • 314-362-3638

  • 1117 and 1118 McMillan Building

  • Bassnett@wustl.edu

  • https://ophthalmology.wustl.edu/items/bassnett-lab/

  • cataract, glaucoma, myopia, microfibrils, imaging, stem cells, Marfan syndrome, fibrillin, modeling, AFM

  • Ocular cell biology

Research Abstract:

We study the development, cell biology, and pathology of the image-forming tissues in the anterior segment of the eye. Small changes in the size or shape of ocular structures can have profound effects on vision but the mechanisms that control the growth and form of ocular tissues are not well understood. We use mathematical models in conjunction with cell lineage tracing and in vivo imaging to understand how the growth of the lens is specified. We are especially interested in the relationship between the physical forces that act on ocular tissues and the growth response of those tissues. For example, mutations in genes encoding proteins of the ciliary zonule (the system of elastic fibers that suspends the lens in the eye) lead to microspherophakia (a lens that is too spherical and too small). How the forces applied to the lens surface by the zonular fibers are transduced into appropriate growth responses is a major area of interest.

The eye also responds to the quality of the images projected onto the retina. A blurred image can cause the axial length of the eye to increase, due to remodeling of collagen molecules in the eye wall (sclera). Every millimeter of excessive growth results in a 3 diopter refractive error. This is the basis of myopia (near sightedness). We are using advanced imaging and single cell RNA sequencing to study the behavior of the fibroblasts that populate the eye wall and participate in scleral remodeling. We hope such studies will guide the development of therapies to prevent or reverse high myopia.

The pressure within the eye is usually carefully regulated. However, certain conditions cause the pressure to increase, leading to retinal damage and vision loss (glaucoma). In conjunction with our clinical colleagues, we are examining one form of glaucoma (exfoliation glaucoma) in which aggregated protein fibrils are produced in the eye. The fibrils accumulate in the drainage structures, causing increased outflow resistance and elevated intraocular pressure. Using mass spectrometry and high resolution electron microscopy we are studying the composition and ultrastructure of the exfoliation material, with the goal of developing methods to disaggregate the fibrils and lower intraocular pressure.

Selected Publications:

Shi, Y., Jones, W., Beatty, W., Tan, Q., Mecham, R.P., Reinhardt, D.P., Gibson, M.A., Reilly, M.A., Rodriguez, J., Bassnett, S. (2021) Latent-transforming growth factor beta-binding protein-2 (LTBP-2) is required for longevity but not for development of zonular fibers. Matrix Biology, 95:15-31. PMCID: PMC8276913.

Bassnett, S. (2021). Zinn's zonule. Progress in Retinal and Eye Research. doi: 10.1016/j.preteyesres.2020.100902. PMCID: PMC8139560.

Jones, W., Rodriguez, J., Bassnett, S. (2019). Targeted deletion of fibrillin-1 in the mouse eye results in ectopia lentis and other ocular phenotypes associated with Marfan syndrome. Disease Models and Mechanisms. doi:10.1242/dmm.037283. PMCID: PMC6361150.

Majtan, T., Jones, W., Krijt, J., Park, I., Kruger, W.D., Kozich, V., Bassnett, S., & Kraus, J.P. (2018) Enzyme replacement therapy ameliorates multiple symptoms of murine homocystinuria. Molecular Therapy, 26(3):834-844. PMCID: PMC5910661.

De Maria, A., Zhao, H.,& Bassnett, S. (2018) Expression of potassium-dependent sodium-calcium exchanger in developing mouse lens. Experimental Eye Research, 167:18-24. PMCID:PMC6811377.

Vinberg, F., Wang, T., De Maria, A., Zhao, H., Bassnett, S., Chen, J., & Kefalov, V. (2017). The Na+/Ca2+, K+ exchanger NCKX4 is required for efficient cone-mediated vision. Elife. e24550. PMCID: PMC5515578.

Šikić, H., & Bassnett, S. (2017). The lens growth process. Progress in Retinal and Eye Research, 60:181-200. PMCID:PMC5605917.

De Maria, A., Wilmarth, P.A., David, L.L., & Bassnett, S. (2017) Proteomic analysis of the bovine and human ciliary zonule. Investigative Ophthalmology and Visual Sciences 58(1):573-585. PMCID:PMC5283081.


Last Updated: 8/4/2021 5:13:05 PM

The ciliary zonule (shown here in blue) is a system of extracellular fibrillin-rich fibers that suspends the lens in the eye. Mutations in genes encoding zonular components have catastrophic effects on vision and underlie conditions such as Marfan syndrome and Weill-Marchesani syndrome.
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