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P. Russell, J. Last, Y. Ding, T. Pan, T. Acott, K. Keller, M. Fautsch, C. J. Murphy; Compliance and the Human Trabecular Meshwork: Implications About Glaucoma. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3205.
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Compliance (inverse of stiffness) is a physical parameter that has profound effects on a number of cell behaviors. We compared the compliance of human trabecular meshwork (HTM) from normal donor tissue and glaucomatous tissue in order to mathematically model the impact of changes in compliance of the juxtacanalicular layer of HTM on flow dynamics through this region.
Atomic force microscopy measured the elastic modulus of HTMs employing the Hertz equation. Changes in moduli of HTM cells cultured on glass (30 GPa) and on hydrogels (3 kPa) were also measured. Using these results, a model was developed that simulated the juxtacanalicular layer of the HTM as a flexible membrane with imbedded pores.
The average value of the elastic modulus from six normal donor HTM samples was 3.5 kPa. The average modulus from six glaucomatous HTMs was 108.7 kPa. This represents about a 30 fold increase in the stiffness of the HTM with glaucoma. The average age of normal donors was 65.6 years while the average for glaucomatous donors was 82.5 years. When HTM cells were grown on glass, they were five times less compliant than when grown on hydrogels. The mathematical model suggests that the resistance to flow through the pores is dependent on flow rate but will increase from around 8 mmHg at modulus values comparable to normal HTM to values of 30 mmHg or greater when modulus values are similar to the glaucomatous HTM.
The data indicate that compliance of glaucomatous HTM is significantly decreased compared with normal HTM. The results with HTM cells show that cells will also change their modulus with changes in compliance of their substrate and implies HTM cells will become stiffer in the glaucomatous HTM. The mathematical model suggests that the changes in the modulus values of the HTM observed in glaucomatous tissue will have profound effects on the resistance to outflow of aqueous humor.
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