[Future Innovative Medicine for Corneal Diseases].

Abstract

Japan faces an aging population and a declining birth rate, so medical professionals and the public are seeking next-generation ophthalmological treatments to preserve and restore visual function. Two fields lie at the heart of this future concept of ophthalmological treatments. The first is predictive medicine and early intervention and treatment. This field is based on precision medicine to treat chronic conditions such as keratoconus, glaucoma, and macular degeneration while the condition is latent or soon after it has developed. The second field is regenerative therapy. This field includes cell therapy, regenerative medicine, artificial corneas and retinal implants. Precision medicine is the concept of examining the effects of genomic information and environmental factors on the onset or progression of a condition. Precision medicine involves dividing patients with a given condition into subgroups and then developing an appropriate method of preventing or treating that condition for each group. This may prove useful in treating corneal conditions such as keratoconus and dry eye. To accomplish that goal, however, overarching genomic, imaging, and biomarker studies must be conducted. Markers related to the onset or progression of a condition must also be identified. This paper describes results of preliminary study of 2 types of markers: biomarkers, and genetic markers. These markers have been used in efforts to predict the onset or progression of keratoconus. The development of regenerative medicine requires basic studies of stem cells and microenvironments (niches) in which to sustain those cells. N-cadherin is a cell adhesion molecule, and the current authors are the first to contend that this molecule plays an important role in the corneal epithelial stem cell niche. In addition, the current authors are the first to report that corneal endothelial cells expressing p75 may potentially be corneal endothelial precursor cells. Capitalizing on the results of that basic study, the current authors have also worked to develop regenerative therapies for the corneal epithelium and the corneal endothelium. The current authors developed the world's first autologous oral mucosal cell sheets to treat corneal epithelial stem cell deficiency. Having conducted a first-in-human clinical study and a multi-center clinical study, the current authors have initiated a physician-led clinical trial of this therapy. In order to identify ways to better restore visual acuity, the current authors are using iPS cells to develop a regenerative therapy with autologous corneal epithelium. Furthermore, the current authors are working to develop a regenerative therapy for corneal endothelium using allogeneic corneal endothelial cells derived from iPS cells. Making medicine of the future a current reality is not easy. Innovations that benefit patients are developed over decades. The current authors hope to pass this baton of scientific innovation on to future generations.