| Vision is our primary means of sensing our environment, and our visual acuity is largely dependent on the quality of the eye's optical components, namely the lens and the cornea. In terrestrial vertebrates, the cornea fulfills a dual role. As part of the eye's outer shell, it acts as a protective lens cover, shielding the delicate inner parts of the eye, maintaining ocular integrity and intraocular pressure. The cornea is also an integral part of the eye's optical system, providing the majority of the eye's refractive power. This dual function requires both structural strength and precise control of corneal shape, which directly influences its optical quality. This shape is controlled by the structure and biomechanics of the collagenous extracellular matrix of the cornea.;We have developed a second harmonic generation based optical imaging paradigm called Non-Linear Optical High Resolution Macroscopy (HRMac) capable of imaging large cross-sectional volumes of corneal collagen at sub-micron resolution in three dimensions. Using HRMac, we have shown that stromal collagen fibers are organized into a complex, highly intertwined three-dimensional meshwork of fibers that increases stromal stiffness and controls corneal shape. We have also developed an automated method to rapidly quantify the collagen fibers' angular orientation, allowing us to characterize the three-dimensional distribution of transverse collagen fibers in human corneas. Our analysis revealed that transverse fibers are distributed heterogeneously across the anterior cornea, which we hypothesize to have a stabilizing effect on corneal shape and biomechanics.;By expanding our studies to include animal corneas from major vertebrate phyla, we have begun to map the evolution of corneal structure and shape and have found marked structural differences between mammalian and non-mammalian corneas.;Finally, we have developed a novel, micropatternable, optically accessible mechanobioreactor capable of recapitulating the mechanical conditions of early ocular development in an effort to understand the influence of mechanical cues on collagen fiber alignment and deposition. |
