Using an open-source modeling software program called CompuCell3D developed by the Biocomplexity Institute in collaboration with the University of Washington and the University of Wisconsin under National Institutes of Health funding, the team quickly began extending existing simulations to study the effects of adhesion defects.
"The simulations showed that reduced adhesion in the retina could indeed lead to its invasion by blood vessels," Shirinifard said. "But the complex structure of the retina meant that many types of adhesion could be important -- the three most prominent being between the pigmented retinal cells (the black lining of the eye) and Bruch's membrane (the substrate that supports the retina), between adjacent pigmented retinal cells, and between pigmented retinal cells and the overlying photoreceptors."
Those variables, the team realized, could be independent of one another or interact in complex ways, and knowing that the rate and type of progression of the disease varies greatly from patient to patient, they needed to examine many examples of each adhesion combination.
That's when Quarry, the IU computer cluster operated by the Office of the Vice President for Information Technology, was called in to push out 32,000 hours of calculations.
"We were able to model the interactions of different degrees of impairment of each type of adhesion and the variation from case to case," Shirinifard said. "Amazingly, these simulations were able to replicate the complex spectrum of CNV seen in the clinic."
Simulations of adhesion defects caused by reduced adhesion between pigmented retinal cells and Bruch's membrane -- the type of CNV typical of aging -- produced a pattern and frequency of invasion agreeing with that in the clinic. Similarly, reduced adhesion between neighboring pigmented retinal cells, typical of inflammation due to severe infection, produced a pattern of
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