A distributed integral control mechanism for regulation of cholesterol concentration in the human retina DOI Creative Commons
Ronél Scheepers, Noa L. Levi, Robyn P. Araujo

et al.

Royal Society Open Science, Journal Year: 2024, Volume and Issue: 11(10)

Published: Oct. 1, 2024

Tight homeostatic control of cholesterol concentration within the complex tissue microenvironment retina is hallmark a healthy eye. By contrast, dysregulation biochemical mechanisms governing retinal homeostasis likely contributes to aetiology and progression age-related macular degeneration (AMD). While signalling maintaining cellular are well-studied, systems-level description molecular interactions regulating balance human remains elusive. Here, we provide comprehensive overview all currently-known molecular-level involved in regulation across major compartments retina, encompassing pigment epithelium (RPE), photoreceptor cell layer, Müller layer Bruch’s membrane. We develop chemical reaction network (CRN) these interactions, involving 71 species, partitioned into 10 independent subnetworks. These subnetworks collectively ensure robust 14 forms distinct compartments. mathematical evidence that three antithetic integral feedback controllers tightly regulate ER cells, with additional extending this other throughout retina. Our novel model provides framework for understanding diseased eyes exploring potential therapeutic strategies.

Language: Английский

Updates on protein-prenylation and associated inherited retinopathies DOI Creative Commons
Sudhat Ashok, Sriganesh Ramachandra Rao

Frontiers in Ophthalmology, Journal Year: 2024, Volume and Issue: 4

Published: July 4, 2024

Membrane-anchored proteins play critical roles in cell signaling, cellular architecture, and membrane biology. Hydrophilic are post-translationally modified by a diverse range of lipid molecules such as phospholipids, glycosylphosphatidylinositol, isoprenes, which allows their partition anchorage to the membrane. In this review article, we discuss biochemical basis isoprenoid synthesis, mechanisms isoprene conjugation proteins, functions prenylated neural retina. Recent discovery novel prenyltransferases, protein chaperones, non-canonical prenylation-target motifs, reversible prenylation is expected increase number inherited systemic blinding diseases with aberrant prenylation. important investigations have also demonstrated role several unexpected regulators (such charge, sequence/protein-chaperone interaction, light exposure history) photoreceptor trafficking proteins. Technical advances investigation proteome its application vision research discussed. Clinical updates technical insights into known putative prenylation-associated retinopathies provided herein. Characterization retina retina-specific fundamental understanding pathogenesis disorders.

Language: Английский

Citations

3

A distributed integral control mechanism for regulation of cholesterol concentration in the human retina DOI Creative Commons
Ronél Scheepers, Noa L. Levi, Robyn P. Araujo

et al.

Royal Society Open Science, Journal Year: 2024, Volume and Issue: 11(10)

Published: Oct. 1, 2024

Tight homeostatic control of cholesterol concentration within the complex tissue microenvironment retina is hallmark a healthy eye. By contrast, dysregulation biochemical mechanisms governing retinal homeostasis likely contributes to aetiology and progression age-related macular degeneration (AMD). While signalling maintaining cellular are well-studied, systems-level description molecular interactions regulating balance human remains elusive. Here, we provide comprehensive overview all currently-known molecular-level involved in regulation across major compartments retina, encompassing pigment epithelium (RPE), photoreceptor cell layer, Müller layer Bruch’s membrane. We develop chemical reaction network (CRN) these interactions, involving 71 species, partitioned into 10 independent subnetworks. These subnetworks collectively ensure robust 14 forms distinct compartments. mathematical evidence that three antithetic integral feedback controllers tightly regulate ER cells, with additional extending this other throughout retina. Our novel model provides framework for understanding diseased eyes exploring potential therapeutic strategies.

Language: Английский

Citations

1