Biology subjects

Celiker, C.

Publications and source records attributed to Celiker, C..

4 recordsLinked to original sources

bioRxiv2025

Photostimulation Improves Maturation of Human Photoreceptors

The human retina contains photoreceptor cells that detect light and enable vision. The development of these cells involves a tightly regulated cascade of structural and molecular events, and their dysfunction leads to irreversible blindness in many retinal diseases. Human retinal organoids derived from stem cells have become powerful tools to model retinal development and disease, but they often remain immature and lack key features required for full function. Light is not only the sensory target of photoreceptors but also an important developmental signal in vivo. However, light has rarely been used as a deliberate stimulus during in vitro differentiation. Here we show that exposing retinal organoids to rhythmic light flicker at a specific frequency enhances photoreceptor maturation across multiple levels. This stimulation improves the development of outer segments, accelerates the transcriptional transition from precursor to mature photoreceptors, and strengthens functional connectivity with downstream neurons. These findings identify patterned light as a potent and physiologically relevant signal for driving retinal development in vitro. This approach represents a non-invasive and easily scalable method for improving the quality of retinal organoids, with implications for disease modelling, drug discovery and the preparation of photoreceptors for cell-based therapies.

cell biology↗

bioRxiv2025

Unveiling the Cellular and Molecular Mechanisms of Diabetic Retinopathy with Human Retinal Organoids

Diabetic retinopathy (DR) is a leading cause of vision impairment worldwide, driven by chronic hyperglycaemia and its complex metabolic consequences. While animal models have been widely used to study DR, they often fail to replicate the physiology of human retina. To address this limitation, we employed human retinal organoids as a model to study the effects of hyperglycaemia across various stages of retinal differentiation. Early-stage organoids demonstrated resilience to high glucose levels, maintaining normal morphology, viability, and gene expression. However, advanced-stage organoids displayed significant disruptions, including the downregulation of outer segment-specific genes, which impaired photoreceptor maturation, and a noticeable shortening of photoreceptor outer segments. Transcriptomic analysis revealed substantial changes in pathways related vision including G protein-coupled receptor signalling pathway, response to light stimulus, and visual perception. While photoreceptors were particularly vulnerable, other retinal cell types, including bipolar cells, ganglion cells, and Muller glia, showed greater resilience. Additionally, glial activation, evidenced by increased expression of astrocyte markers, suggested an adaptive response to hyperglycaemia. To validate our findings, we compared our dataset with publicly available transcriptomic datasets from human retinas with DR, confirming key overlaps in pathways related to photoreceptor dysfunction, gliogenesis, and oxidative stress responses. These results establish human retinal organoids as an effective and relevant model for studying the molecular mechanisms of neurodegeneration associated with DR progression.

cell biology↗

bioRxiv2023

Light-Responsive MicroRNAs in Human Retinal Tissue are Differentially Regulated by Distinct Wavelengths of Light

Retinal microRNA (miRNA) molecules play critical roles in a wide range of processes including cell proliferation, cell death, and synaptic plasticity. Recently they have been shown to regulate crucial processes that are associated with perception of light including visual function, light adaptation, and control of genes regulating circadian light entrainment. Despite extensive work on retinal miRNAs in different model organisms, light-regulated miRNAs in human retina are not known. Here, we aim to characterize these miRNAs. We generated light responsive human retinal organoids that express miRNA families and clusters typically found in the retina. Using in-house-developed photostimulation device, we found that 51 miRNAs are up- or downregulated upon brief photostimulation periods. Clustering analysis revealed that only two miRNA families and three clusters are upregulated, while eight families and ten cluster are downregulated upon photostimulation. Additionally, we found that the light-regulated miRNAs have rapid turnover, and their expression is differentially regulated by distinct wavelengths of light. This study demonstrates that only a small subset of miRNAs is light-responsive in human retinal tissue and the generated human retinal organoids are a valuable model for studying the molecular mechanisms of light perception in the retina.

cell biology↗

bioRxiv2022

LuminoCell: a versatile and affordable luminometer platform for monitoring in-cell luciferase-based reporters

Luciferase reporter assays represent a simple and sensitive experimental system in cell and molecular biology to study multiple biological processes. However, the application of these assays is often limited by the costs of conventional luminometer instruments and the versatility of their use in different experimental conditions. Therefore, we aimed to develop a small, affordable luminometer allowing continuous measurement of luciferase activity, designed for inclusion into various kinds of tissue culture incubators. Here we introduce LuminoCell - an open-source platform for the construction of an affordable, sensitive, and portable luminometer capable of realtime monitoring in-cell luciferase activity. The LuminoCell costs $40, requires less than 1 hour to assemble, and it is capable of performing real-time sensitive detection of both magnitude and duration of the activity of major signalling pathways in cell cultures, including receptor tyrosine kinases (EGF, FGF), WNT/{beta}-catenin, and NF-{kappa}B. Additionally, we show that the LuminoCell is suitable to be used in cytotoxicity assays as well as for monitoring periodic circadian gene expression.

molecular biology↗