⚙
AI-generated deep summary
by claude@2026-07, 2026-07-04
· read from full text
ⓘ
The study investigates how cell loss disrupts mechanical homeostasis and contributes to an ageing-like phenotype in postmitotic retinal pigment epithelium (RPE) using reductionistic in vitro monolayers derived from postmitotic stem cells. By inducing large-scale apoptosis, the authors observed structural hallmarks of aged RPE, including reduced cell height, shortened microvilli, and cytoskeletal reorganization, alongside a new mechanical equilibrium characterized by tissue stiffening and increased junctional contractility. Functionally, the apoptotic monolayers showed impaired phagocytosis of photoreceptor outer segments, and actin-nucleator modulation indicated that apicolateral deformation is critical for phagocytosis and becomes compromised when mechanical homeostasis shifts. The paper emphasizes that structural remodeling alone can impair tissue function independent of other stressors, and it is framed as an in vitro model with careful distinction from in vivo ageing implications. The paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.
Abstract
Tissue homeostasis relies on mechanical feedback loops balanced by cell loss and proliferation. However, maintaining this balance becomes particularly challenging in postmitotic tissues, where alternative mechanisms replace compensatory proliferation. In the postmitotic retinal pigment epithelium (RPE), these mechanisms include significant structural adaptations over time. Yet, how these adaptations relate to epithelial mechanical homeostasis and age-associated functional decline remains poorly understood. To establish the relationship between structural changes, mechanical homeostasis and function, we developed an in vitro reductionistic model mimicking age-related reduction in RPE cell density. Inducing large-scale apoptosis in postmitotic stem cell-derived RPE monolayers recapitulates structural hallmarks of aged tissue, such as reduced cell height, shortened microvilli and cytoskeletal reorganisation. This new structure acquires a new mechanical equilibrium, evidenced by tissue stiffening and enhanced junctional contractility. Functionally, the monolayers display impaired vision-supporting phagocytosis of photoreceptor outer segments. Mechanistically, modulation of actin nucleators, Arp2/3 and formins, demonstrates that apicolateral monolayer deformation is critical for phagocytosis and may be compromised in aged RPE. Our findings suggest that a shift in mechanical homeostasis due to cell loss is a major driver of age-related RPE functional decline. Importantly, we show that structural remodelling in ageing alone can compromise tissue function, independent of other stressors.
Full text
2,158 characters
· extracted from
oa-doi-fallback
· click to expand
Abstract
Tissue homeostasis relies on mechanical feedback loops balanced by cell loss and proliferation. However, maintaining this balance becomes particularly challenging in postmitotic tissues, where alternative mechanisms replace compensatory proliferation. In the postmitotic retinal pigment epithelium (RPE), these mechanisms include significant structural adaptations over time. Yet, how these adaptations relate to epithelial mechanical homeostasis and age-associated functional decline remains poorly understood. To establish the relationship between structural changes, mechanical homeostasis and function, we developed an in vitro reductionistic model mimicking age-related reduction in RPE cell density. Inducing large-scale apoptosis in postmitotic stem cell-derived RPE monolayers recapitulates structural hallmarks of aged tissue, such as reduced cell height, shortened microvilli and cytoskeletal reorganisation. This new structure acquires a new mechanical equilibrium, evidenced by tissue stiffening and enhanced junctional contractility. Functionally, the monolayers display impaired vision-supporting phagocytosis of photoreceptor outer segments. Mechanistically, modulation of actin nucleators, Arp2/3 and formins, demonstrates that apicolateral monolayer deformation is critical for phagocytosis and may be compromised in aged RPE. Our findings suggest that a shift in mechanical homeostasis due to cell loss is a major driver of age-related RPE functional decline. Importantly, we show that structural remodelling in ageing alone can compromise tissue function, independent of other stressors.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
We have changed the following: - We improved the clarity of our narrative and more clearly emphasised the novelty of our work. - We significantly reduced speculative statements regarding in vitro ageing, and we now clearly distinguish confirmed findings from potential implications for understanding in vivo ageing. - We updated the title and abstract to better reflect the core outcomes and significance of the study. - We added new control experiments.
Text is read by the "Ask this paper" AI Q&A widget below.
Extraction quality varies by source — PMC NXML preserves structure
cleanly, OA-HTML may include some navigation residue, and OA-PDF can
have broken hyphenation. The publisher copy
(via DOI)
is the canonical version.