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Apoptosis during macrophage-dependent ocular tissue remodelling
1Skirball Institute for Biomolecular Medicine, Developmental Biology and Genetics, New York University Medical Center, NY 10016.
Abstract:
We have characterized the nature and pattern of cell death during regression of the pupillary membrane, a developmentally transient capillary network found in the anterior chamber of the eye. This analysis has revealed that the cellular components of the pupillary membrane include vascular endothelial cells in an intricate network of fine capillaries as well as attendant macrophages. The capillaries are situated on the anterior surface of the lens and held in relative position by a cobweb-like meshwork of extracellular matrix fibres that regress along with the cellular components of this structure. Cell death during regression of the pupillary membrane is characteristic of apoptosis. Specifically, apoptotic bodies containing condensed chromatin can be observed in vascular endothelial cells and genomic DNA isolated from the pupillary membrane shows the nucleosomal fragmentation pattern typical of apoptotic cells. Using a method for labelling fragmented DNA in tissue preparations (TUNEL), we have assessed the overall pattern of apoptotic cell death during pupillary membrane regression. We find that apoptosis occurs either in single cells in healthy vessels or synchronously along the entire length of a capillary segment. Both morphological and TUNEL analysis indicate that capillary regression occurs from junction to junction one segment at a time. We propose a model to explain the pattern of capillary regression observed and conclude from these and previous experiments (Lang and Bishop (1993) Cell 74, 453-462), that during regression of the pupillary membrane, the macrophage elicits target cell death by inducing apoptosis.
Insights
The pupillary membrane
Area of Science:
- Ophthalmology
- Developmental Biology
- Cell Biology
Background:
- The pupillary membrane is a transient vascular network in the anterior eye chamber.
- It comprises capillaries, endothelial cells, extracellular matrix, and macrophages.
- Understanding its regression is key to ocular development.
Purpose of the Study:
- To characterize cell death during pupillary membrane regression.
- To elucidate the pattern and mechanism of capillary regression.
- To determine the role of macrophages in this process.
Main Methods:
- Morphological analysis of pupillary membrane regression.
- Identification of apoptotic bodies and condensed chromatin.
- TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labeling) assay for fragmented DNA.
- Genomic DNA fragmentation analysis.
Main Results:
- Cell death during regression is primarily apoptosis.
- Apoptosis occurs in single cells or synchronously along capillary segments.
- Capillary regression proceeds segment by segment.
- Macrophages induce apoptosis in target cells.
Conclusions:
- Pupillary membrane regression involves macrophage-induced apoptosis.
- Capillary regression follows a specific junction-to-junction pattern.
- This study provides a model for understanding vascular regression during development.