Glaucoma Cell Biology Laboratory
Department of Ophthalmology and Visual Sciences

 

Trabecular Meshwork Stress and Regeneration

 







 

 

 

Trabecular Meshwork cell stress impedes function of the tissue


Elevated intraocular pressure is a significant risk factor for the development of glaucoma. The trabecular meshwork (TM) is vital in the regulation of IOP.

Our studies have shown that expression of damaged or mutated proteins in trabecular meshwork cells can lead to cellular stress that eventually results in the death of the cell. TM cell stress can also be brought about by environmental factors or simply by advanced age. The loss of TM cells in glaucoma has been documented, but it has not been directly demonstrated that reduced TM cell function or cellularity results in loss of IOP control.

Can the glaucomatous trabecular meshwork be repaired?

We believe that replacement of damaged or lost trabecular meshwork (TM) cells with healthy cells leads to functional restoration following transplantation into glaucoma eyes. The source of these cells is, of course, crucial. In order to avoid immune rejection reactions to the transplanted tissue, it is desirable to use cells harvested from the patient. A patientís native TM cells are difficult to obtain and may additionally be functionally compromised due to the effects of age-related stresses. In collaboration with laboratories here at the University of Iowa Institute for Vision Research we are investigating if TM-like cells generated from induced pluripotent stem cell (iPSC-TM) can be used for this purpose. These cells can be created from the patientís own dermal fibroblasts which are easily obtained through a skin biopsy.

So far our results have been very promising. We have transplanted iPSC-TM into transgenic mice expressing a gene known to cause trabecular meshwork dysfunction, elevated IOP, and glaucoma in humans. Following transplantation aqueous humor outflow facility incresed and the IOP decreased in recipient mice. This led to enhanced survival of retinal ganglion cells, which is a very good indicator that the transplantation preserved vision.

This approach, which eliminates many of the ethical and practical concerns associated with the use of stem cells, offers a clinically feasible solution to this challenge. Successful trabecular meshwork restoration would permanently restore IOP control and thereby reduce costs related to the life-long management of this chronic disease.

iPSC-TM carrying out phagocytosis

Microscopy image of trabecular meshwork cells created from induced pluripotent stem cells. Here the cells, which we call iPSC-TM, have taken up particles, seen as bright green spots, in a process called phagocytosis. The size, shape, and functionality of the cells are dramatically different from the originating stem cells.

 

 

Cell stress can compromise TM cell function and control of IOP

 

 

Perfusion Organ Culture

Changes in trabecular meshwork function can be measured using an organ culture system

 

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