Glucocorticoids Preferentially Influence Expression of Nucleoskeletal Actin Network and Cell Adhesive Proteins in Human Trabecular Meshwork Cells.


Clinical use of glucocorticoids is associated with increased intraocular pressure (IOP), a major risk factor for glaucoma. Glucocorticoids have been reported to induce changes in actin cytoskeletal organization, cell adhesion, extracellular matrix, fibrogenic activity, and mechanical properties of trabecular meshwork (TM) tissue, which plays a crucial role in aqueous humor dynamics and IOP homeostasis. However, we have a limited understanding of the molecular underpinnings regulating these myriad processes in TM cells. To understand how proteins, including cytoskeletal and cell adhesion proteins that are recognized to shuttle between the cytosolic and nuclear regions, influence gene expression and other cellular activities, we used proteomic analysis to characterize the nuclear protein fraction of dexamethasone (Dex) treated human TM cells. Treatment of human TM cells with Dex for 1, 5, or 7 days led to consistent increases (by ≥ two-fold) in the levels of various actin cytoskeletal regulatory, cell adhesive, and vesicle trafficking proteins. Increases (≥two-fold) were also observed in levels of Wnt signaling regulator (glypican-4), actin-binding chromatin modulator (BRG1) and nuclear actin filament depolymerizing protein (MICAL2; microtubule-associated monooxygenase, calponin and LIM domain containing), together with a decrease in tissue plasminogen activator. These changes were independently further confirmed by immunoblotting analysis. Interestingly, deficiency of BRG1 expression blunted the Dex-induced increases in the levels of some of these proteins in TM cells. In summary, these findings indicate that the widely recognized changes in actin cytoskeletal and cell adhesive attributes of TM cells by glucocorticoids involve actin regulated BRG1 chromatin remodeling, nuclear MICAL2, and glypican-4 regulated Wnt signaling upstream of the serum response factor/myocardin controlled transcriptional activity.





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Publication Info

Bachman, William, Rupalatha Maddala, Ayon Chakraborty, Camelia Eldawy, Nikolai P Skiba and Ponugoti V Rao (2022). Glucocorticoids Preferentially Influence Expression of Nucleoskeletal Actin Network and Cell Adhesive Proteins in Human Trabecular Meshwork Cells. Frontiers in cell and developmental biology, 10. p. 886754. 10.3389/fcell.2022.886754 Retrieved from

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Rupalatha Maddala

Assistant Professor of Ophthalmology

Dr. Maddala was recently promoted to Associate Professor of Ophthalmology following her
post-doctoral fellowship and research scientist roles in the Rao Laboratory. She has a keen
interest in fundamental biological research. Her research is focused on ocular lens and
glaucoma. Dr. Maddala's post doctorial research demonstrated the essential role of Rho, Rac
and Rap1 GTPases in lens development and function.

During her time as a research scientist, her research discovered that the lens expresses S100A4,
a small molecular calcium binding protein which exhibits a lens fiber cell-specific, discrete
distribution profile, an independent research project that was NIH-funded.

Dr. Maddala’s long term plans include understanding lens and trabecular meshwork (TM)
biology and function as they relate to ocular dysfunction and identification of new therapies to
address unmet needs in ocular disease. She has been invited to present her research at ISER
meetings in Berlin and Montreal, Lens and Cataract meeting of NFER in Hawaii and ARVO
annual conferences. She also enjoys teaching undergraduate, medical and postdoctorial


Nikolai Petrovich Skiba

Associate Professor of Ophthalmology

My research focuses on applying mass spectrometry based proteomics to study proteins in eye tissues, cells and sub-cellular compartments to understand mechanisms of vision. An important aspect of my research is to identify proteins in different compartments of retinal photoreceptor cells, their amount and modification status at different cell states defined by the light conditions, genotype, disease etc. This information can be valuable in understanding molecular mechanisms of vision and biology of the photoreceptor cell. Another important aspect of my research is to assist basic scientist and clinicians in our department in their proteomic needs which include identification of proteins and other biomolecules in a given biological sample, detection of protein post-translational modifications and sequence variations, elucidation of protein-protein interactions and also characterization of changes in the protein concentration and composition in a biological sample at different conditions.


Ponugoti Vasantha Rao

Richard and Kit Barkhouser Distinguished Professor

Research in our laboratory focuses on two areas of ocular diseases- cataract and glaucoma.

As it relates to lens biology, we are investigating cytoskeletal signaling pathways critical for lens development, cytoarchitecture, shape and function. Ongoing studies are focused on identification and characterization of plasma membrane cytoskeletal scaffolding proteins (e.g. Periaxin, ankyrins and dystrophin/dystroglycan) involved in regulation of lens fiber cell shape, alignment, tensile properties, membrane domain organization and channel protein activity, and to determine how dysregulation of membrane cytoskeletal scaffolding activity impacts these determinants of lens structure and function. Our studies are based on using both in vitro and in vivo models, and application of high resolution microscopy, mass spectrometry, biochemical and gene targeting approaches.

In the context of glaucoma, we are exploring the cellular and molecular mechanisms involved in homeostasis of intraocular pressure and aqueous humor drainage with the ultimate goal of identifying novel molecular targets upon which to base the design of therapeutic glaucoma treatments.  Our laboratory is currently studying the extracellular and intracellular mechanisms (e.g. GDF-15, extracellular kinases and phosphatases, Rho GTPase/Rho kinase and the Autotaxin-LPA axis) that control cell morphology, cell adhesive interactions, plasticity, transdifferentiation, extracellular matrix synthesis, phosphorylation and organization, fibrosis and contractile properties of the trabecular meshwork, and aqueous humor outflow and intraocular pressure. These studies utilize both in vitro and in vivo models, and a combination of trabecular meshwork-derived primary cultures, perfusion studies, high resolution microscopy, mass spectrometry, biochemical, physiological and gene targeting approaches.

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