Biology subjects

Bailly, M.

Publications and source records attributed to Bailly, M..

3 recordsLinked to original sources

bioRxiv2025

Interdependent regulation of trabecular meshwork cell physiology and intraocular pressure by KALRN and TMCO1

Glaucoma is a leading cause of irreversible blindness. Primary open-angle glaucoma (POAG) is its most common form. Higher intraocular pressure (IOP), resulting from impaired aqueous humour outflow, is the cardinal mediating factor, and all proven treatments aim to lower IOP. POAG is a complex genetic disease with numerous loci linked to POAG and higher IOP. The mechanisms by which risk alleles cause disease remain unclear. Here, using primary trabecular meshwork (TM) cells, a cell type controlling outflow, and mice, we found that the POAG-associated gene KALRN encodes an endoplasmic reticulum (ER)-associated Rac regulator essential for TM homeostasis and normal IOP. KALRN loss caused widespread disruption from ER to calcium homeostasis and energy metabolism, leading to induction of cell senescence. KALRN-depletion also led to suppression of the ER translocase and calcium regulator TMCO1, encoded by a gene at one of the most significantly associated genomic loci for POAG. TMCO1-depletion in vitro and in vivo phenocopied KALRN-induced phenotypes, and reduced KALRN expression. These findings establish KALRN and TMCO1 as interdependent regulators of TM homeostasis and IOP, that link regulation of ER and intracellular calcium homeostasis to cell and tissue physiology, and illustrate how different genes linked to glaucoma can form regulatory pathways.

cell biology↗

bioRxiv2025

Dopamine selectively regulates pediatric sclera/choroid interactions through the stimulation of exosome-associated retinoic acid

Postnatal eye growth is critical for healthy vision and yet, how this process is regulated at the cellular level is still unclear. The choroid is thought to play a crucial role in relaying signals from the retina to the sclera to modulate eye growth, but which cells are targeted and how they interact is not known. Using primary cultures of pediatric and adult human choroid and sclera stromal fibroblasts, we investigated the effect of choroid-conditioned medium (CCM) on scleral fibroblasts contractile activity. We show that CCM activates pediatric scleral fibroblast contraction, with age and antero-posterior location differences. Upon exposure to dopamine, a known negative regulator of eye growth, pediatric - but not adult - choroid cells lose their ability to stimulate scleral fibroblasts. Using RNA-Sequencing, we show that dopamine stimulates pathways linked to ribosomal activation, translation and exosome release exclusively in pediatric choroid cells. Removing exosomes from the CCM rescued the ability of dopamine-treated choroid cells to stimulate scleral fibroblasts. We further identify retinoic acid as the active exosome-associated compound preventing scleral fibroblast activation. Mechanistically, we show that CCM stimulates actomyosin-mediated protrusive activity in scleral fibroblasts. This is prevented when scleral cells are exposed to dopamine-CCM, and fully rescued upon exosome removal or ALDH1 inhibition. We thus propose that pediatric choroid stromal cells specifically relay dopamine-mediated retinal signals to the sclera during post-natal eye growth, operating through changes in secretome - including the production of exosome-associated retinoic acid - rather than gene expression changes. SIGNIFICANCEEye size is critical to optimal vision but the exact cellular and molecular mechanisms regulating it are still unknown. Failure to properly regulate postnatal eye growth leads to elongated eyes and myopia. Myopia is expected to affect half of the world population by 2050, with many at risk of blinding complications. Eye growth and homeostasis are supported by the sclera and the choroid, but how the two tissues interact to regulate eye growth is unknown. We use here human cells to demonstrate direct, age-specific, interactions between the two cell types and provide a rationale for the known negative effect of dopamine on eye growth, with significant implications for future studies as well as for the understanding and treatment of myopia.

cell biology↗

bioRxiv2018

Rab27a co-ordinates actin-dependent transport by controlling organelle-associated motors and track assembly proteins.

Cell biologists generally consider that microtubules and actin play complementary roles in long- and short-distance transport in animal cells. On the contrary, using melanosomes of melanocytes as a model, we recently discovered that motor myosin-Va, works with dynamic actin tracks, to drive long-range organelle dispersion in microtubule depleted cells. This suggests that in animals, as in yeast and plants, myosin/actin can drive long-range transport. Here we show that SPIRE1/2 and formin-1 (FMN1) proteins generate actin tracks required for myosin-Va-dependent transport in melanocytes. Moreover we show that, in addition to melanophilin/myosin-Va, Rab27a can recruit SPIRE1/2 to melanosomes, thereby integrating motor and track assembly activity at the organelle membrane. Based on this we suggest a model in which organelles and force generators (motors and track assemblers) are linked forming a cell-wide network that allows their collective activity to rapidly disperse the population of organelles long-distance throughout the cytoplasm.

cell biology↗