Generation of a Double Reporter mES Cell Line to Simultaneously Trace the Generation of Retinal Progenitors and Photoreceptors.

Three-dimensional retinal culture systems help to understand eye development and the pathology of disorders. There is a need for reporter stem cell lines to allow in vitro studies on retinal progenitors and photoreceptors and their developmental dynamics or properties and to test therapeutic approaches. The isolation of pure progenitor populations or photoreceptor precursors may serve for drug, gene, and cell therapy development.

Exploring Histone Modifications in Inherited Retinal Disorders.

Inherited retinal disorders (IRD) represent a heterogeneous group of retinal diseases, mainly leading to a progressive photoreceptor cell death, and for which almost no treatment exists. Despite the diversity in genetic components of IRD, several studies evidence the activation of common cellular pathways, regulated by epigenetic modifications. Since these ones are reversible, a growing interest emerges in proposing a gene-agnostic approach to treat IRD through epigenetic modulation.

Glutamylation imbalance impairs the molecular architecture of the photoreceptor cilium.

Microtubules, composed of conserved α/β-tubulin dimers, undergo complex post-translational modifications (PTMs) that fine-tune their properties and interactions with other proteins. Cilia exhibit several tubulin PTMs, such as polyglutamylation, polyglycylation, detyrosination, and acetylation, with functions that are not fully understood. Mutations in AGBL5, which encodes the deglutamylating enzyme CCP5, have been linked to retinitis pigmentosa, suggesting that altered polyglutamylation may cause photoreceptor cell degeneration, though the underlying mechanisms are unclear.

Fine-tuning FAM161A gene augmentation therapy to restore retinal function.

For 15 years, gene therapy has been viewed as a beacon of hope for inherited retinal diseases. Many preclinical investigations have centered around vectors with maximal gene expression capabilities, yet despite efficient gene transfer, minimal physiological improvements have been observed in various ciliopathies. Retinitis pigmentosa-type 28 (RP28) is the consequence of bi-allelic null mutations in the FAM161A, an essential protein for the structure of the photoreceptor connecting cilium (CC).