{"doi":"10.1002/cne.901570303","title":"The relationship between morphogenetic cell death and the development of congenital anophthalmia","abstract":"<jats:title>Abstract</jats:title><jats:p>Glücksmann ('51) observed that during normal mammalin ocular morphogenesis large numbers of cells become necrotic and are resorbed within the eye rudiment prior to and during invagination of the optic cup. Silver and Hughes ('73) observed that these resorptions are largely confined to the ventral aspect of the optic rudiment where the optic fissure subsequently forms. Evidence for the role of cell death during fissure formation and other morphogenetic events during eye development has remained unclear, however, since the quantity of degenerate cells cannot be selectively controlled in developing tissue by experimental means (Saunders, '66).</jats:p><jats:p>Chase et al. ('41a) described a congenitally anophthalmic strain of mice in which, he proposed, retarded growth of the eye vesicle and the consequent failure of lens induction result in approximately 90% eyeless and 10% microphthalmic neonates. Upon reexamination of a sequence of embryos of the eyeless strain it was observed that during the earliest stages of ocular morphogenesis the regular sequence of necrotic loci, which Silver and Hughes ('73) have described in rat and other mammalin embryos, is entirely lacking.</jats:p><jats:p>Our observations suggest that the first recognizable divergence between the morphology of timed mutant (strain zrdct‐an) and control embryos (strain C57BL/6J) occurs during apposition of the optic vesicle and surface ectoderm but prior to the development of the retinal thickening and lens placode. In control embryos mesenchyme which becomes entrapped between the prospective retina and lens becomes necrotic and is resorbed. Conversely, in eyeless embryos the surfaces of the presumptive retina and lens, while closely apposed, are separated by variable numbers of mesenchymal cells which remain viable and can undergo mitoses throughout development. The failure of mesenchymal cells to degenerate may lead to the reduction in size of both retina and lens primordia. Contrary to Chase's ('41a) observations, in all anophthalmic embryos contact between the optic vesicle and lens epithelium is eventually established and a lens of variable size is induced. In most cases, however, the lens is displaced from the eye chamber by proliferation of the mesenchymal cell mass and the optic rudiment is subsequently resorbed. In the remaining embryos which presumably will become microphthalmic the lens reaches a critical dimension and is retained within the eye cup. In them, although cell death is absent from within the developing eye vesicle and cup, invagination can proceed as far as the retinal fissure stage. However, the optic fissure does not form. These observations suggest that there may be a relationship between morphogenetic cell death, formation of the optic fissure, and the production of severe congenital eye defects.</jats:p>","journal":"Journal of Comparative Neurology","year":1974,"id":22755,"datarank":9.249449631062642,"base_score":4.672828834461906,"endowment":4.672828834461906,"self_citation_contribution":0.7009243251692859,"citation_network_contribution":8.548525305893357,"self_endowment_contribution":0.7009243251692859,"citer_contribution":8.548525305893357,"corpus_percentile":null,"corpus_rank":null,"citation_count":106,"citer_count":99,"citers_with_citation_signal":90,"citers_with_endowment":90,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":142036,"name":"A. F. W. Hughes","orcid":null,"position":1,"is_corresponding":false},{"id":142035,"name":"J. Silver","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":4.672828834461906,"endowment":4.672828834461906,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"4423725","pmcid":null,"openalex_id":"https://openalex.org/W2113650922","authors":[],"funders":[],"total_grants":0,"fwci":4.2361,"citation_percentile":0.94046835,"influential_citations":0,"citation_trend":[{"year":2014,"count":1},{"year":2019,"count":1},{"year":2025,"count":1},{"year":2026,"count":1}],"oa_status":"closed","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fcne.901570303","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/cne.901570303","host_type":"publisher"},{"url":"https://doi.org/10.1002/cne.901570303","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/4423725","host_type":"repository"},{"url":"https://mouseion.jax.org/ssbb1974/860","host_type":"repository"}],"fields_of_study":["Ocular Disorders and Treatments","Connexins and lens biology","Cell Adhesion Molecules Research","Medicine","Biology","Animals","Anophthalmos","Cell Survival","Eye","Mice","Mice, Inbred C57BL","Morphogenesis"],"mesh_terms":["Animals","Anophthalmos","Cell Survival","Eye","Mice, Inbred C57BL","Morphogenesis","Mice"],"keywords":["Optic vesicle","Biology","Optic cup (embryology)","Eye development","Retina","Morphogenesis","Anophthalmia","Anatomy","Lens (geology)","Embryo","Embryology","Neural plate","Neurulation","Apposition","Cell biology","PAX6","Embryogenesis","Microphthalmia","Genetics","Gastrulation","Neuroscience","Phenotype"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-07T15:59:21.603584Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}