A groundbreaking study led by researchers at NYU Langone Health has unveiled the potential of three-dimensional, lab-grown "mini-corneas" in advancing the study of corneal diseases. These mini-corneas closely resemble the developing human cornea, offering a powerful tool for researchers to explore various corneal disorders, which rank as the third leading cause of blindness.
The study, published in PNAS Nexus, not only sheds light on the molecular events underlying corneal development in the womb but also holds promise for developing improved therapies and cell-based regenerative treatments for corneal diseases.
The researchers embarked on this study to create corneal organoids, distinct from traditional cell cultures, where stem cells are grown in a nutrient-rich environment with specific adjustments to allow for the development and organization of multiple cell types in a three-dimensional structure. This innovative technology better mimics the structure and functionality of actual corneal tissues, enabling a more accurate representation for research purposes.
Dr. Shukti Chakravarti, a professor in the Departments of Ophthalmology and Pathology at NYU Grossman School of Medicine and corresponding study author, emphasizes, "Our study is the first to examine human corneal organoids at a single-cell resolution. By deciphering the genetic code expressed by active genes in this model, we have discovered that our organoids closely resemble maturing corneas found in the womb."
Key to the study's findings is gene expression, the process whereby activated genes encode molecular instructions in DNA, which are then converted into messenger RNA to build the proteins necessary for cell function within tissues. The NYU Langone team employed single-cell RNA sequencing to identify genes specific to various cell types in both lab-derived human corneal organoids and adult human corneas from cadavers.
The results revealed that adult corneas primarily consist of epithelial cells (outer layer), stromal cells (middle layer), and a small number of endothelial cells (innermost layer). In contrast, the organoids displayed a substantial presence of cells across all three layers, with approximately one-third to one-fourth of the developing cells exhibiting an endothelial signature. Interestingly, the activated gene signature of the organoids closely resembled that of developing immature corneas.
Dr. Chakravarti remarks, "These organoids offer an opportunity to study gene expression during development. With their 3D structures and coexisting cell types, they provide a more natural environment to investigate cellular signaling and cell-cell interactions."
Beyond enhancing our understanding of human cornea development, the study organoids hold significant potential for future genetic disease screening and the exploration of potential therapies. Importantly, the use of these organoids could reduce costs associated with traditional mouse model studies.
In addition to Dr. Chakravarti, the research involved the contributions of several other NYU Langone authors, including George Maiti, PhD, and Nan Hu, MS, from the Department of Ophthalmology; Igor Dolgalev, PhD, from the Applied Bioinformatics Laboratories; and Aristotelis Tsirigos, PhD, from the Applied Bioinformatics Laboratories, as well as the Departments of Medicine and Pathology.
Collaborators from other institutions include Maithê Rocha Monteiro de Barros, DVM, PhD, from Columbia University; Mona Roshan, MD, and Karl J. Wahlin, PhD, from the University of California, San Diego; and James W. Foster, PhD, from Johns Hopkins School of Medicine. Funding for the study was provided by National Institutes of Health grants R01EY030917 and R01EY026104.