A multidisciplinary study by researchers at the Doheny Eye Institute, an affiliate of the University of California Los Angeles (UCLA), in collaboration with vision researchers at the University of California Irvine, has revealed an entirely new mechanism behind the early loss of retinal capillaries in diabetes.
Using atomic force microscopy, a technique originally developed for physics and materials science research, they demonstrated that retinal capillaries in diabetic mice become stiffer in the early stages. Crucially, blocking this stiffening inhibited capillary degeneration and mitigated the loss of contrast sensitivity, a common visual defect in early diabetic retinopathy (DR) patients.
Having identified the protein (lysyl oxidase) responsible for the increase in retinal capillary stiffness, the researchers administered an oral drug to diabetic mice that inactivated lysyl oxidase, successfully blocking capillary stiffening. Further investigation into the mechanism revealed that stiffer capillaries become more adhesive and sensitive to toxic immune cells that contribute to DR development, resulting in increased capillary cell death.
These promising findings showcase the potential of an oral drug to inhibit retinopathy, thus eliminating the need for repeated eye injections, and introducing retinal capillary stiffness as a new target for DR prevention strategies.
This work was supported by multiple grants from the NEI/NIH, The Stephen Ryan Initiative for Macular Research (RIMR), a special grant from the W.M. Keck Foundation, and unrestricted grants from Research to Prevent Blindness, Inc. to the Department of Ophthalmology at UCLA and Gavin Herbert Eye Institute at UC Irvine.