The cornea is avascular, which makes it an excellent model to study matrix protein expression and tissue stiffness. The corneal epithelium adheres to the basement zone and the underlying stroma is composed of keratocytes and an extensive matrix of collagen and proteoglycans. Our goal was to examine changes in corneas of 8- and 15-week mice and compare them to 15-week pre-Type 2 diabetic obese mouse. Nanoindentation was performed on corneal epithelium in situ and then the epithelium was abraded, and the procedure repeated on the basement membrane and stroma. Confocal imaging was performed to examine the localization of proteins. Stiffness was found to be age and obesity dependent. Young’s modulus was greater in the epithelium from 15-week mice compared to 8-week mice. At 15 weeks, the epithelium of the control was significantly greater than that of the obese mice. There was a difference in the localization of Crb3 and PKCζ in the apical epithelium and a lack of lamellipodial extensions in the obese mouse. In the pre-Type 2 diabetic obese mouse there was a difference in the stiffness slope and after injury localization of fibronectin was negligible. These indicate that age and environmental changes incurred by diet alter the integrity of the tissue with age rendering it stiffer. The corneas from the pre-Type 2 diabetic obese mice were significantly softer and this may be a result of changes both in proteins on the apical surface indicating a lack of integrity and a decrease in fibronectin.

Purpose Choroideremia (CHM) is an X-linked inherited retinal degeneration causing loss of the photoreceptors, retinal pigment epithelium, and choriocapillaris, although patients typically retain a central island of relatively preserved, functioning retina until late-stage disease. Here, we investigate cone photoreceptor morphology within the retained retinal island by examining cone inner segment area, density, circularity, and intercone space. Methods Using a custom-built, multimodal adaptive optics scanning light ophthalmoscope, nonconfocal split-detection images of the photoreceptor mosaic were collected at 1°, 2°, and 4° temporal to the fovea from 13 CHM and 12 control subjects. Cone centers were manually identified, and cone borders were segmented. A custom MATLAB script was used to extract area and circularity for each cone and calculate the percentage of intercone space in each region of interest. Bound cone density was also calculated. An unbalanced two-way ANOVA and Bonferroni post hoc tests were used to assess statistical differences between the CHM and control groups and along retinal eccentricity. Results Cone density was lower in the CHM group than in the control group ( P < 0.001) and decreased with eccentricity from the fovea ( P < 0.001). CHM cone inner segments were larger in area ( P < 0.001) and more circular ( P = 0.042) than those of the controls. Intercone space in CHM was also higher than in the controls ( P < 0.001). Conclusions Cone morphology is altered in CHM compared to control, even within the centrally retained, functioning retinal area. Further studies are required to determine whether such morphology is a precursor to cone degeneration.