ANR Project CorMecha - ANR-21-CE19-0010

Link to ANR Project CorMecha - ANR-21-CE19-0010

Multiscale mapping and biomechanics of healthy and pathological Human corneas

Objective and main issues

The cornea is a unique tissue featuring several important physiological properties, mainly transparency and refraction related to crucial biomechanical properties. It exhibits a viscoelastic behavior which is important for maintaining the corneal curvature despite changes in intraocular pressure and various forces applied on cornea, such as external shocks or eye rubbing. Corneal biomechanical properties are closely related to the structure of stroma (fig. 1A), which consists of several hundred 1-3 µm thick stacked lamellae made of collagen fibrils (25-30 nm of diameter) aligned and regularly packed to ensure cornea transparency. Lamellae are organized parallel to each other in the posterior part of the corneal stroma with a steep change in the direction of fibrils between two adjacent lamellae, whereas the organization of the anterior stroma is more complex, with interwoven lamellae.
This project aims to set up an atlas of 3D corneal structure from the sub-micrometer scale (intra-lamellar organization of collagen fibrils) to the millimeter-centimeter scale (lamellae distribution in the full cornea), and to accurately measure the associated biomechanical properties linked to this structure, in physiological conditions and in various pathological conditions, including high intra-ocular pressure and keratoconic corneas (localized corneal thinning and steepening with decreased biomechanical strength). The main underlying hypothesis is that the corneal biomechanical properties are closely related to the multiscale organization of collagen fibrils in the stroma, which is a common assumption in all connective tissues, based both on experimental evidence and on numerical simulations of biomechanical response. The ultimate goals are two-fold:
- to translate this structural atlas obtained by advanced multiphoton microscopy into easily-detectable features using common techniques in clinical ophthalmology. It will be based on multimodal imaging of the same corneas using usual topographic tools, clinical and advanced OCTs, confocal and multiphoton microscopies, as well as dedicated bioimage informatics tools.
- to build a model of corneal biomechanics based on this structural atlas and the mechanical measures in order to understand the role of specific stromal microstructures and to serve in the long run as a predictive tool by clinicians, mainly to improve refractive surgery.

Partners

The LOB (Laboratory of Optics and Biosciences) is a joint CNRS - INSERM - Ecole Polytechnique research unit in Palaiseau working at the interface between physics and biology. The group of Marie-Claire Schanne-Klein published the first multimodal multiphoton images of human cornea, the first in vivo multiphoton images of rat cornea and is a leader in experimental implementation and quantitative processing of polarization-resolved SHG images. Moreover, the group has complementary expertise in bioimage informatics with the recent release of a quantitative geometry package for Python and in tissue culture . Finally, the group benefits from the state-of-the-art imaging facility and expertise of the Morphoscope equipex at LOB.

The  group of Vincent Borderie at INSERM-DGOS CIC 1423 (Sorbonne Université, CHNO des 15-20) works on corneal physiology through multimodal imaging of normal (human and animal) and diseased human corneas. The group also has an expertise in corneal biology and stem cells, which is complementary to the physical approach of corneal physiology.

The group of Jean-Marc Allain at LMS (Laboratoire de Mécanique des Solides, joint CNRS - Mines ParisTech - Ecole Polytechnique research unit in Palaiseau) has been working on soft tissue mechanics for a decade both experimentally and theoretically. The group developed new testing machines dedicated to in situ assays under optical or electronic microscopes. He concurrently developed an expertise in the extraction of relevant mechanical data from 2D and 3D images by use of custom-made software, and in the development of models that derive mechanical behavior at macroscopic scale from the microstructure, including fibrous microstructure.

Publications

Borderie, V.; Beauruel, J.; Cuyaubère, R.; Georgeon, C.; Memmi, B.; Sandali, O. Comprehensive Assessment of Corvis ST Biomechanical Indices in Normal and Keratoconus Corneas with Reference to Corneal Enantiomorphism. J. Clin. Med. 2023, 12, 690 - 10.3390/jcm12020690

C. Raoux, A. Chessel, P. Mahou, G. Latour, and M.-C. Schanne-Klein, "Unveiling the lamellar structure of the human cornea over its full thickness using polarization-resolved SHG microscopy," Light: Science and Applications 12, 190 (2023) - 10.1038/s41377-023-01224-0