Identification of Small Molecules for Prevention of Lens Epithelium-Derived Cataract Using Zebrafish
Cataract is the leading cause of blindness worldwide. It can be treated by surgery, whereby the damaged crystalline lens is replaced by a synthetic lens. Although cataract surgery is highly effective, a relatively common complication named posterior capsular opacification (PCO) leads to secondary lo...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-10-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/21/2540 |
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| author | Kineret Taler Nour Zatari Mohammad Iqbal Lone Shahar Rotem-Bamberger Adi Inbal |
| author_facet | Kineret Taler Nour Zatari Mohammad Iqbal Lone Shahar Rotem-Bamberger Adi Inbal |
| author_sort | Kineret Taler |
| collection | DOAJ |
| description | Cataract is the leading cause of blindness worldwide. It can be treated by surgery, whereby the damaged crystalline lens is replaced by a synthetic lens. Although cataract surgery is highly effective, a relatively common complication named posterior capsular opacification (PCO) leads to secondary loss of vision. PCO is caused by abnormal proliferation and migration of residual lens epithelial cells (LECs) that were not removed during the surgery, which results in interruption to the passage of light. Despite technical improvements to the surgery, this complication has not been eradicated. Efforts are being made to identify drugs that can be applied post-surgery, to inhibit PCO development. Towards the goal of identifying such drugs, we used zebrafish embryos homozygous for a mutation in <i>plod3</i> that develop a lens phenotype with characteristics of PCO. Using both biased and unbiased approaches, we identified small molecules that can block the lens phenotype of the mutants. Our findings confirm the relevance of zebrafish <i>plod3</i> mutants’ lens phenotype as a model for lens epithelium-derived cataract and add to our understanding of the molecular mechanisms that contribute to the development of this pathology. This understanding should help in the development of strategies for PCO prevention. |
| first_indexed | 2024-03-11T11:32:54Z |
| format | Article |
| id | doaj.art-af96db1f77304ccf82690273b7abcc99 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T11:32:54Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-af96db1f77304ccf82690273b7abcc992023-11-10T15:00:42ZengMDPI AGCells2073-44092023-10-011221254010.3390/cells12212540Identification of Small Molecules for Prevention of Lens Epithelium-Derived Cataract Using ZebrafishKineret Taler0Nour Zatari1Mohammad Iqbal Lone2Shahar Rotem-Bamberger3Adi Inbal4Department of Medical Neurobiology, Institute for Medical Research—Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem 9112002, IsraelDepartment of Medical Neurobiology, Institute for Medical Research—Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem 9112002, IsraelDepartment of Medical Neurobiology, Institute for Medical Research—Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem 9112002, IsraelDepartment of Medical Neurobiology, Institute for Medical Research—Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem 9112002, IsraelDepartment of Medical Neurobiology, Institute for Medical Research—Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem 9112002, IsraelCataract is the leading cause of blindness worldwide. It can be treated by surgery, whereby the damaged crystalline lens is replaced by a synthetic lens. Although cataract surgery is highly effective, a relatively common complication named posterior capsular opacification (PCO) leads to secondary loss of vision. PCO is caused by abnormal proliferation and migration of residual lens epithelial cells (LECs) that were not removed during the surgery, which results in interruption to the passage of light. Despite technical improvements to the surgery, this complication has not been eradicated. Efforts are being made to identify drugs that can be applied post-surgery, to inhibit PCO development. Towards the goal of identifying such drugs, we used zebrafish embryos homozygous for a mutation in <i>plod3</i> that develop a lens phenotype with characteristics of PCO. Using both biased and unbiased approaches, we identified small molecules that can block the lens phenotype of the mutants. Our findings confirm the relevance of zebrafish <i>plod3</i> mutants’ lens phenotype as a model for lens epithelium-derived cataract and add to our understanding of the molecular mechanisms that contribute to the development of this pathology. This understanding should help in the development of strategies for PCO prevention.https://www.mdpi.com/2073-4409/12/21/2540zebrafish<i>plod3</i>Lysyl hydroxylase 3cataractposterior capsular opacificationsmall molecule screen |
| spellingShingle | Kineret Taler Nour Zatari Mohammad Iqbal Lone Shahar Rotem-Bamberger Adi Inbal Identification of Small Molecules for Prevention of Lens Epithelium-Derived Cataract Using Zebrafish Cells zebrafish <i>plod3</i> Lysyl hydroxylase 3 cataract posterior capsular opacification small molecule screen |
| title | Identification of Small Molecules for Prevention of Lens Epithelium-Derived Cataract Using Zebrafish |
| title_full | Identification of Small Molecules for Prevention of Lens Epithelium-Derived Cataract Using Zebrafish |
| title_fullStr | Identification of Small Molecules for Prevention of Lens Epithelium-Derived Cataract Using Zebrafish |
| title_full_unstemmed | Identification of Small Molecules for Prevention of Lens Epithelium-Derived Cataract Using Zebrafish |
| title_short | Identification of Small Molecules for Prevention of Lens Epithelium-Derived Cataract Using Zebrafish |
| title_sort | identification of small molecules for prevention of lens epithelium derived cataract using zebrafish |
| topic | zebrafish <i>plod3</i> Lysyl hydroxylase 3 cataract posterior capsular opacification small molecule screen |
| url | https://www.mdpi.com/2073-4409/12/21/2540 |
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