Investigation of human organoid retina with digital holographic transmission matrix measurements

Abstract

Advanced manufacturing of retinal organoid samples from human induced pluripotent stem cells represents a promising way to study the development of retinal diseases. The retina is an epithelium composed of different cell layers with unique optical properties and detects light by photoreceptor neurons for visual function. There are still many challenges in detecting early and distinct cellular changes in retinal disease. In this paper, we study the capability of the optical transmission matrix, which fully describes the transition of a light field propagating through a scattering sample. Despite its rich information content, the transmission matrix is commonly just used for light delivery through scattering media. Digital holography is employed to measure the complex light-field information of the transmitted light. We demonstrate that singular value decomposition of the transmission matrix allows to discriminate phantom tissues with varying scattering coefficient. We apply these findings to retinal organoid tissues. Application of the protonophore carbonyl cyanide m-chloro-phenylhydrazone (CCCP), a known inducer of retinal damage in animals, caused cell death and structural changes in human retinal organoids, which resulted in distinct changes in the transmission matrix. Our data indicate that the analysis of the transmission matrix can distinguish pathologic changes of the retina towards the development of imaging-based biomarkers.