Project SummaryGlaucoma is the 2nd leading cause of blindness worldwide as 7 million people are blind from this condition.There have been extensive studies concluding that primary open angle glaucoma (POAG) has a higherprevalence in populations of both African descent and Hispanic ethnicity. The mechanical theory of glaucomarests on the assumption that mechanical damage forces acting on the optic nerve cause a loss of retinalganglion cell function. While there is evidence that the extracellular matrix of the lamina cribrosa (LC) andperipapillary sclera (PS) remodel in the presence of glaucoma this remodeling has not been extensivelyquantified in certain higher risk populations (aged African Descent (AD) Hispanic Ethnicity (HE)). Preferentialdifferences in the PS microstructure and mechanical properties of these populations may provide a mechanismby which POAG can occur at normal IOPs. The current research proposal will investigate the relationshipbetween PS and LC matrix microstructure and mechanical properties seeking to identify how theserelationships are affected by race/ethnicity and age. The central hypothesis of the proposed work is thatdifferences in the microstructure and mechanical properties of the LC and PS exist as a function ofrace/ethnicity and age. These changes are hypothesized to play a role in the higher prevalence of glaucoma inpopulations of AD and HE compared with those of European Descent (ED) independent of the level ofintraocular pressure. While the extracellular matrix microstructures of the LC and PS have been investigated previously howsuch organization relates to the mechanical function of these tissues is not currently understood. This isprimarily due to the fact that nearly all quantification of this microstructural information has resulted fromhistological studies which rely on snap freezing or fixing the tissue in an embedding medium (thus precludingsimultaneous mechanical characterization). We have recently developed a micro-optomechanical (MOMD)device which is capable of simultaneously measuring the matrix organization of unfixed LC and PS while thesetissues undergo mechanical deformations. The MOMD excites the second harmonic generation of collagenand the two-photon emitted fluorescence of elastin while simultaneously exposing posterior ocular tissues toeither planar biaxial or pressure-inflation loads. The three primary aims of this project are to identify differences(as a function of race/ethnicity and age) in 1) the microstructural organization of the human LC at various IOPs;2) the biomechanical response and microstructure the human PS at various IOPs; and 3) the biomechanicalenvironment of posterior ocular tissues using microstructurally-based computational simulations. Providing adetailed account of age and ethnicity associated differences in LC and PS microstructure and mechanicalproperties may provide a unique opportunity for the development of novel diagnosis and treatmentopportunities.