Choroidal melanocyte secretome from cultured cells and tissue-engineered choroid models exposed to acute or chronic oxidative stress
Bibliographic record
Abstract
The choroid, located between the retina and the sclera, is a vascularized and pigmented connective tissue, playing a crucial role in providing oxygen and nutrients to the outer layers of the retina, and in absorbing excessive light. How choroidal melanocytes (CMs) participate in tissue homeostasis through paracrine signaling with neighboring cells is poorly understood. In this study, using two-dimensional and three-dimensional models, we aimed to identify proteins secreted by CMs under different oxidative stress conditions. To do so, CMs, choroidal fibroblasts (CFs), and retinal pigment epithelial (RPE) cells were isolated from native human RPE/choroidal tissues and expanded. RNA was isolated and processed for gene profiling analysis. The self-assembly approach of tissue engineering was used to form 3D stromal substitutes, and RPE cells and/or CMs were added to produce 3D models with different cell combinations. The medium conditioned by cells in 2D and 3D cultures was collected in a non-stressed condition and following acute or chronic oxidative stress exposures, then proteome and ELISA analyses were performed to identify cytokines secreted majorly by CMs. RNA analysis revealed 15 secretome-related transcripts that were more abundantly expressed in CMs compared to the other 2 cell types, including serpin family F member 1 (SERPINF1) (coding for pigment epithelium-derived factor; PEDF) and secreted phosphoprotein 1 (SPP1) (coding for osteopontin). At the protein level, the expression of osteopontin and PEDF was higher in CMs of different age groups compared to CFs and RPE cells. In the 3D models containing CMs, cytokine arrays also identified macrophage inflammatory protein (MIP)-1α/MIP-1β in non-stressed, MIP-1α/MIP-1β, interleukin (IL)-24, and angiogenin following an acute oxidative stress, and macrophage migration inhibitory factor (MIF), granulocyte-colony stimulating factor (G-CSF), intercellular adhesion molecule-1 (ICAM-1), and IL-1α following a chronic oxidative stress. This study identifies for the first time trophic factors secreted by CMs that could influence neighboring cells through paracrine signaling. Of those, PEDF and osteopontin are antioxidative proteins that are known to attenuate oxidative stress damage. Identifying factors that can help manage oxidative stress in the posterior segment of the eye may lead to promising treatments for retinal diseases.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".