Citation:

# Investigation of human organoid retina with digital holographic transmission matrix measurements

• Light: Advanced Manufacturing  3, Article number: 4 (2022)
• 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.

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###### 通讯作者: 陈斌, bchen63@163.com
• 1.

沈阳化工大学材料科学与工程学院 沈阳 110142

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### Research Summary

Transmission matrix: Label-free biomarker for detection of degeneration in retinal organoids

Retinal organoids derived from human induced pluripotent stem cells are three-dimensional organ-like systems that enable new paths to understand the mechanisms of retinal degenerative diseases. Routinely, label-based methods are used for classification of organoid’s health status. As retinal disease most often is accompanied by cellular changes and loss of tissue structure, we study whether the scattering properties can act as label-free biomarker. Therefore, we determine and mathematically evaluate the optical transmission matrix, which connects defined input light fields with output light fields after interaction with a scattering sample. Pathologic changes in human retinal organoids were induced with the application of the protonophore CCCP. Our data show first evidence that transmission matrix analysis enables distinguishing pathologic changes of the retina compared to a healthy control group and thus has potential to act as label-free biomarker.

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## Investigation of human organoid retina with digital holographic transmission matrix measurements

• 1. Laboratory for Measurement and Sensorsystem Technique, TU Dresden, Dresden, Germany
• 2. Competence Center for Biomedical Laser Systems (BIOLAS), TU Dresden, Dresden, Germany
• 3. Center for Regenerative Therapies Dresden (CRTD), TU Dresden, Dresden, Germany
• 4. German Center for Neurodegenerative Diseases (DZNE) Dresden, Dresden, Germany
• 5. Faculty of Physics, TU Dresden, Dresden, Germany
• 6. Excellence Cluster Physics of Life (PoL), TU Dresden, Dresden, Germany
###### Jürgen W. Czarske, juergen.czarske@tu-dresden.de
• These authors contributed equally: Nektarios Koukourakis, Felix Wagner

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.

### Research Summary

Transmission matrix: Label-free biomarker for detection of degeneration in retinal organoids

Retinal organoids derived from human induced pluripotent stem cells are three-dimensional organ-like systems that enable new paths to understand the mechanisms of retinal degenerative diseases. Routinely, label-based methods are used for classification of organoid’s health status. As retinal disease most often is accompanied by cellular changes and loss of tissue structure, we study whether the scattering properties can act as label-free biomarker. Therefore, we determine and mathematically evaluate the optical transmission matrix, which connects defined input light fields with output light fields after interaction with a scattering sample. Pathologic changes in human retinal organoids were induced with the application of the protonophore CCCP. Our data show first evidence that transmission matrix analysis enables distinguishing pathologic changes of the retina compared to a healthy control group and thus has potential to act as label-free biomarker.

show all

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