Killing two birds with one stone: dual blockade of integrin and FGF signaling through targeting syndecan-4 in postoperative capsular opacification
The most common complication after cataract surgery is postoperative capsular opacification, which includes anterior capsular opacification (ACO) and posterior capsular opacification (PCO). Increased adhesion of lens epithelial cells (LECs) to the intraocular lens material surface promotes ACO forma...
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| creator | Qin, Yingyan Zhu, Yi Luo, Furong Chen, Chuan Chen, Xiaoyun Wu, Mingxing |
| description | The most common complication after cataract surgery is postoperative capsular opacification, which includes anterior capsular opacification (ACO) and posterior capsular opacification (PCO). Increased adhesion of lens epithelial cells (LECs) to the intraocular lens material surface promotes ACO formation, whereas proliferation and migration of LECs to the posterior capsule lead to the development of PCO. Cell adhesion is mainly mediated by the binding of integrin to extracellular matrix proteins, while cell proliferation and migration are regulated by fibroblast growth factor (FGF). Syndecan-4 (SDC-4) is a co-receptor for both integrin and FGF signaling pathways. Therefore, SDC-4 may be an ideal therapeutic target for the prevention and treatment of postoperative capsular opacification. However, how SDC-4 contributes to FGF-mediated proliferation, migration, and integrin-mediated adhesion of LECs is unclear. Here, we found that downregulation of SDC-4 inhibited FGF signaling through the blockade of ERK1/2 and PI3K/Akt/mTOR activation, thus suppressing cell proliferation and migration. In addition, downregulation of SDC-4 suppressed integrin-mediated cell adhesion through inhibiting focal adhesion kinase (FAK) phosphorylation. Moreover, SDC-4 knockout mice exhibited normal lens morphology, but had significantly reduced capsular opacification after injury. Finally, SDC-4 expression level was increased in the anterior capsule LECs of age-related cataract patients. Taken together, we for the first time characterized the key regulatory role of SDC-4 in FGF and integrin signaling in human LECs, and provided the basis for future pharmacological interventions of capsular opacification. |
| doi_str_mv | 10.1038/cddis.2017.315 |
| format | Article |
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Increased adhesion of lens epithelial cells (LECs) to the intraocular lens material surface promotes ACO formation, whereas proliferation and migration of LECs to the posterior capsule lead to the development of PCO. Cell adhesion is mainly mediated by the binding of integrin to extracellular matrix proteins, while cell proliferation and migration are regulated by fibroblast growth factor (FGF). Syndecan-4 (SDC-4) is a co-receptor for both integrin and FGF signaling pathways. Therefore, SDC-4 may be an ideal therapeutic target for the prevention and treatment of postoperative capsular opacification. However, how SDC-4 contributes to FGF-mediated proliferation, migration, and integrin-mediated adhesion of LECs is unclear. Here, we found that downregulation of SDC-4 inhibited FGF signaling through the blockade of ERK1/2 and PI3K/Akt/mTOR activation, thus suppressing cell proliferation and migration. In addition, downregulation of SDC-4 suppressed integrin-mediated cell adhesion through inhibiting focal adhesion kinase (FAK) phosphorylation. Moreover, SDC-4 knockout mice exhibited normal lens morphology, but had significantly reduced capsular opacification after injury. Finally, SDC-4 expression level was increased in the anterior capsule LECs of age-related cataract patients. Taken together, we for the first time characterized the key regulatory role of SDC-4 in FGF and integrin signaling in human LECs, and provided the basis for future pharmacological interventions of capsular opacification.</description><identifier>ISSN: 2041-4889</identifier><identifier>EISSN: 2041-4889</identifier><identifier>DOI: 10.1038/cddis.2017.315</identifier><identifier>PMID: 28703800</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>1-Phosphatidylinositol 3-kinase ; 13/21 ; 13/89 ; 14/19 ; 38/77 ; 45/90 ; 631/80/86 ; 692/699/3161/3168 ; 692/700/565/1436/2185 ; 692/700/565/545 ; 82/80 ; 96/35 ; 96/95 ; Age ; AKT protein ; Animals ; Anterior Chamber - metabolism ; Anterior Chamber - pathology ; Antibodies ; Biochemistry ; Capsule Opacification - metabolism ; Capsule Opacification - pathology ; Capsule Opacification - surgery ; Cataracts ; Cell activation ; Cell adhesion ; Cell adhesion & migration ; Cell Adhesion - drug effects ; Cell Biology ; Cell Culture ; Cell growth ; Cell Line ; Cell Movement - drug effects ; Cell proliferation ; Cell Proliferation - drug effects ; Disease Models, Animal ; Epithelial cells ; Epithelial Cells - cytology ; Epithelial Cells - metabolism ; Extracellular matrix ; Extracellular signal-regulated kinase ; Eye surgery ; Fibroblast Growth Factor 2 - pharmacology ; Fibroblast growth factors ; Focal adhesion kinase ; G1 Phase Cell Cycle Checkpoints - drug effects ; Humans ; Immunology ; Integrins - metabolism ; Kinases ; Lens, Crystalline - cytology ; Life Sciences ; Mice ; Mice, Knockout ; Original ; original-article ; Phosphorylation ; Postoperative period ; Protein Kinases - metabolism ; Retina - metabolism ; Retina - pathology ; RNA Interference ; Signal transduction ; Signal Transduction - drug effects ; Surgery ; Syndecan ; Syndecan-4 - antagonists & inhibitors ; Syndecan-4 - genetics ; Syndecan-4 - metabolism ; TOR protein</subject><ispartof>Cell death & disease, 2017-07, Vol.8 (7), p.e2920-e2920</ispartof><rights>The Author(s) 2017</rights><rights>Copyright Nature Publishing Group Jul 2017</rights><rights>Copyright © 2017 The Author(s) 2017 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c458t-1cd3260e99456249370fc4b18c493bab5319ad05e6f2c4ab59548e5a41ba40493</citedby><cites>FETCH-LOGICAL-c458t-1cd3260e99456249370fc4b18c493bab5319ad05e6f2c4ab59548e5a41ba40493</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5550862/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5550862/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,27905,27906,41101,42170,51557,53772,53774</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28703800$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Qin, Yingyan</creatorcontrib><creatorcontrib>Zhu, Yi</creatorcontrib><creatorcontrib>Luo, Furong</creatorcontrib><creatorcontrib>Chen, Chuan</creatorcontrib><creatorcontrib>Chen, Xiaoyun</creatorcontrib><creatorcontrib>Wu, Mingxing</creatorcontrib><title>Killing two birds with one stone: dual blockade of integrin and FGF signaling through targeting syndecan-4 in postoperative capsular opacification</title><title>Cell death & disease</title><addtitle>Cell Death Dis</addtitle><addtitle>Cell Death Dis</addtitle><description>The most common complication after cataract surgery is postoperative capsular opacification, which includes anterior capsular opacification (ACO) and posterior capsular opacification (PCO). Increased adhesion of lens epithelial cells (LECs) to the intraocular lens material surface promotes ACO formation, whereas proliferation and migration of LECs to the posterior capsule lead to the development of PCO. Cell adhesion is mainly mediated by the binding of integrin to extracellular matrix proteins, while cell proliferation and migration are regulated by fibroblast growth factor (FGF). Syndecan-4 (SDC-4) is a co-receptor for both integrin and FGF signaling pathways. Therefore, SDC-4 may be an ideal therapeutic target for the prevention and treatment of postoperative capsular opacification. However, how SDC-4 contributes to FGF-mediated proliferation, migration, and integrin-mediated adhesion of LECs is unclear. Here, we found that downregulation of SDC-4 inhibited FGF signaling through the blockade of ERK1/2 and PI3K/Akt/mTOR activation, thus suppressing cell proliferation and migration. In addition, downregulation of SDC-4 suppressed integrin-mediated cell adhesion through inhibiting focal adhesion kinase (FAK) phosphorylation. Moreover, SDC-4 knockout mice exhibited normal lens morphology, but had significantly reduced capsular opacification after injury. Finally, SDC-4 expression level was increased in the anterior capsule LECs of age-related cataract patients. Taken together, we for the first time characterized the key regulatory role of SDC-4 in FGF and integrin signaling in human LECs, and provided the basis for future pharmacological interventions of capsular opacification.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>13/21</subject><subject>13/89</subject><subject>14/19</subject><subject>38/77</subject><subject>45/90</subject><subject>631/80/86</subject><subject>692/699/3161/3168</subject><subject>692/700/565/1436/2185</subject><subject>692/700/565/545</subject><subject>82/80</subject><subject>96/35</subject><subject>96/95</subject><subject>Age</subject><subject>AKT protein</subject><subject>Animals</subject><subject>Anterior Chamber - metabolism</subject><subject>Anterior Chamber - pathology</subject><subject>Antibodies</subject><subject>Biochemistry</subject><subject>Capsule Opacification - metabolism</subject><subject>Capsule Opacification - pathology</subject><subject>Capsule Opacification - surgery</subject><subject>Cataracts</subject><subject>Cell activation</subject><subject>Cell adhesion</subject><subject>Cell adhesion & migration</subject><subject>Cell Adhesion - drug effects</subject><subject>Cell Biology</subject><subject>Cell Culture</subject><subject>Cell growth</subject><subject>Cell Line</subject><subject>Cell Movement - drug effects</subject><subject>Cell proliferation</subject><subject>Cell Proliferation - drug effects</subject><subject>Disease Models, Animal</subject><subject>Epithelial cells</subject><subject>Epithelial Cells - cytology</subject><subject>Epithelial Cells - metabolism</subject><subject>Extracellular matrix</subject><subject>Extracellular signal-regulated kinase</subject><subject>Eye surgery</subject><subject>Fibroblast Growth Factor 2 - pharmacology</subject><subject>Fibroblast growth factors</subject><subject>Focal adhesion kinase</subject><subject>G1 Phase Cell Cycle Checkpoints - drug effects</subject><subject>Humans</subject><subject>Immunology</subject><subject>Integrins - metabolism</subject><subject>Kinases</subject><subject>Lens, Crystalline - cytology</subject><subject>Life Sciences</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Original</subject><subject>original-article</subject><subject>Phosphorylation</subject><subject>Postoperative period</subject><subject>Protein Kinases - metabolism</subject><subject>Retina - metabolism</subject><subject>Retina - pathology</subject><subject>RNA Interference</subject><subject>Signal transduction</subject><subject>Signal Transduction - drug effects</subject><subject>Surgery</subject><subject>Syndecan</subject><subject>Syndecan-4 - antagonists & inhibitors</subject><subject>Syndecan-4 - genetics</subject><subject>Syndecan-4 - metabolism</subject><subject>TOR protein</subject><issn>2041-4889</issn><issn>2041-4889</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNptkc9vFCEUx0mjaZu1V4-GxIuX2cIMzDIeTEzjVtMmXvRM3gAzS2VhBKZN_w3_Yll3bbZGDvB47_O-_Pgi9JqSJSWNuFRa27SsCV0tG8pP0HlNGK2YEN2Lo_gMXaR0R8poGlLz9hSd1WJV-gk5R79urHPWjzg_BNzbqBN-sHmDgzc45TK_x3oGh3sX1A_QBocBW5_NGK3H4DVeX69xsqOHvcomhnnc4AxxNHmXSY9eGwW-YqUPT6GITiZCtvcGK5jS7CDiMIGyg1UlHfwr9HIAl8zFYV2g7-tP364-V7dfr79cfbytFOMiV1Tppm6J6TrG25p1zYoMivVUqBL30POGdqAJN-1QK1b2HWfCcGC0B0YKs0Af9rrT3G-NVsbnCE5O0W4hPsoAVj6veLuRY7iXnHMi2roIvDsIxPBzNinLrU3KOAfehDlJ2lEhWNvRVUHf_oPehTmWTztQDemKIwu03FMqhpSiGZ4uQ4ncOS7_OC53jsvieGl4c_yEJ_yvvwW43AOplPxo4tG5_5f8DYh1ucs</recordid><startdate>20170713</startdate><enddate>20170713</enddate><creator>Qin, Yingyan</creator><creator>Zhu, Yi</creator><creator>Luo, Furong</creator><creator>Chen, Chuan</creator><creator>Chen, Xiaoyun</creator><creator>Wu, Mingxing</creator><general>Nature Publishing Group UK</general><general>Springer Nature B.V</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20170713</creationdate><title>Killing two birds with one stone: dual blockade of integrin and FGF signaling through targeting syndecan-4 in postoperative capsular opacification</title><author>Qin, Yingyan ; Zhu, Yi ; Luo, Furong ; Chen, Chuan ; Chen, Xiaoyun ; Wu, Mingxing</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c458t-1cd3260e99456249370fc4b18c493bab5319ad05e6f2c4ab59548e5a41ba40493</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>13/21</topic><topic>13/89</topic><topic>14/19</topic><topic>38/77</topic><topic>45/90</topic><topic>631/80/86</topic><topic>692/699/3161/3168</topic><topic>692/700/565/1436/2185</topic><topic>692/700/565/545</topic><topic>82/80</topic><topic>96/35</topic><topic>96/95</topic><topic>Age</topic><topic>AKT protein</topic><topic>Animals</topic><topic>Anterior Chamber - metabolism</topic><topic>Anterior Chamber - pathology</topic><topic>Antibodies</topic><topic>Biochemistry</topic><topic>Capsule Opacification - metabolism</topic><topic>Capsule Opacification - pathology</topic><topic>Capsule Opacification - surgery</topic><topic>Cataracts</topic><topic>Cell activation</topic><topic>Cell adhesion</topic><topic>Cell adhesion & migration</topic><topic>Cell Adhesion - drug effects</topic><topic>Cell Biology</topic><topic>Cell Culture</topic><topic>Cell growth</topic><topic>Cell Line</topic><topic>Cell Movement - drug effects</topic><topic>Cell proliferation</topic><topic>Cell Proliferation - drug effects</topic><topic>Disease Models, Animal</topic><topic>Epithelial cells</topic><topic>Epithelial Cells - cytology</topic><topic>Epithelial Cells - metabolism</topic><topic>Extracellular matrix</topic><topic>Extracellular signal-regulated kinase</topic><topic>Eye surgery</topic><topic>Fibroblast Growth Factor 2 - pharmacology</topic><topic>Fibroblast growth factors</topic><topic>Focal adhesion kinase</topic><topic>G1 Phase Cell Cycle Checkpoints - drug effects</topic><topic>Humans</topic><topic>Immunology</topic><topic>Integrins - metabolism</topic><topic>Kinases</topic><topic>Lens, Crystalline - cytology</topic><topic>Life Sciences</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Original</topic><topic>original-article</topic><topic>Phosphorylation</topic><topic>Postoperative period</topic><topic>Protein Kinases - metabolism</topic><topic>Retina - metabolism</topic><topic>Retina - pathology</topic><topic>RNA Interference</topic><topic>Signal transduction</topic><topic>Signal Transduction - drug effects</topic><topic>Surgery</topic><topic>Syndecan</topic><topic>Syndecan-4 - antagonists & inhibitors</topic><topic>Syndecan-4 - genetics</topic><topic>Syndecan-4 - metabolism</topic><topic>TOR protein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Qin, Yingyan</creatorcontrib><creatorcontrib>Zhu, Yi</creatorcontrib><creatorcontrib>Luo, Furong</creatorcontrib><creatorcontrib>Chen, Chuan</creatorcontrib><creatorcontrib>Chen, Xiaoyun</creatorcontrib><creatorcontrib>Wu, Mingxing</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell death & disease</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Qin, Yingyan</au><au>Zhu, Yi</au><au>Luo, Furong</au><au>Chen, Chuan</au><au>Chen, Xiaoyun</au><au>Wu, Mingxing</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Killing two birds with one stone: dual blockade of integrin and FGF signaling through targeting syndecan-4 in postoperative capsular opacification</atitle><jtitle>Cell death & disease</jtitle><stitle>Cell Death Dis</stitle><addtitle>Cell Death Dis</addtitle><date>2017-07-13</date><risdate>2017</risdate><volume>8</volume><issue>7</issue><spage>e2920</spage><epage>e2920</epage><pages>e2920-e2920</pages><issn>2041-4889</issn><eissn>2041-4889</eissn><abstract>The most common complication after cataract surgery is postoperative capsular opacification, which includes anterior capsular opacification (ACO) and posterior capsular opacification (PCO). Increased adhesion of lens epithelial cells (LECs) to the intraocular lens material surface promotes ACO formation, whereas proliferation and migration of LECs to the posterior capsule lead to the development of PCO. Cell adhesion is mainly mediated by the binding of integrin to extracellular matrix proteins, while cell proliferation and migration are regulated by fibroblast growth factor (FGF). Syndecan-4 (SDC-4) is a co-receptor for both integrin and FGF signaling pathways. Therefore, SDC-4 may be an ideal therapeutic target for the prevention and treatment of postoperative capsular opacification. However, how SDC-4 contributes to FGF-mediated proliferation, migration, and integrin-mediated adhesion of LECs is unclear. Here, we found that downregulation of SDC-4 inhibited FGF signaling through the blockade of ERK1/2 and PI3K/Akt/mTOR activation, thus suppressing cell proliferation and migration. In addition, downregulation of SDC-4 suppressed integrin-mediated cell adhesion through inhibiting focal adhesion kinase (FAK) phosphorylation. Moreover, SDC-4 knockout mice exhibited normal lens morphology, but had significantly reduced capsular opacification after injury. Finally, SDC-4 expression level was increased in the anterior capsule LECs of age-related cataract patients. Taken together, we for the first time characterized the key regulatory role of SDC-4 in FGF and integrin signaling in human LECs, and provided the basis for future pharmacological interventions of capsular opacification.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>28703800</pmid><doi>10.1038/cddis.2017.315</doi><oa>free_for_read</oa></addata></record> |
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| subjects | 1-Phosphatidylinositol 3-kinase 13/21 13/89 14/19 38/77 45/90 631/80/86 692/699/3161/3168 692/700/565/1436/2185 692/700/565/545 82/80 96/35 96/95 Age AKT protein Animals Anterior Chamber - metabolism Anterior Chamber - pathology Antibodies Biochemistry Capsule Opacification - metabolism Capsule Opacification - pathology Capsule Opacification - surgery Cataracts Cell activation Cell adhesion Cell adhesion & migration Cell Adhesion - drug effects Cell Biology Cell Culture Cell growth Cell Line Cell Movement - drug effects Cell proliferation Cell Proliferation - drug effects Disease Models, Animal Epithelial cells Epithelial Cells - cytology Epithelial Cells - metabolism Extracellular matrix Extracellular signal-regulated kinase Eye surgery Fibroblast Growth Factor 2 - pharmacology Fibroblast growth factors Focal adhesion kinase G1 Phase Cell Cycle Checkpoints - drug effects Humans Immunology Integrins - metabolism Kinases Lens, Crystalline - cytology Life Sciences Mice Mice, Knockout Original original-article Phosphorylation Postoperative period Protein Kinases - metabolism Retina - metabolism Retina - pathology RNA Interference Signal transduction Signal Transduction - drug effects Surgery Syndecan Syndecan-4 - antagonists & inhibitors Syndecan-4 - genetics Syndecan-4 - metabolism TOR protein |
| title | Killing two birds with one stone: dual blockade of integrin and FGF signaling through targeting syndecan-4 in postoperative capsular opacification |
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