Development of a model of elevated intraocular pressure in rats by gene transfer of bone morphogenetic protein 2
To determine whether inducing calcification in the trabecular meshwork results in elevated IOP in living rats. To use this property to create an elevated IOP animal model by gene transfer of bone morphogenetic protein 2 (BMP2). Calcification was assessed by alizarin red staining in primary human tra...
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| Veröffentlicht in: | Investigative ophthalmology & visual science 2013-08, Vol.54 (8), p.5441-5455 |
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| creator | Buie, Lakisha K Karim, Md Zahidul Smith, Matthew H Borrás, Teresa |
| description | To determine whether inducing calcification in the trabecular meshwork results in elevated IOP in living rats. To use this property to create an elevated IOP animal model by gene transfer of bone morphogenetic protein 2 (BMP2).
Calcification was assessed by alizarin red staining in primary human trabecular meshwork (HTM) cells and alkaline phosphatase (ALP) activity in the angle tissue. Brown Norway (BN) and Wistar rats were intracamerally injected with Ad5BMP2 (OS) and control Ad5.CMV-Null (OD). IOPs were taken twice a week and expressed as mean integral pressures. Morphology was assessed on fixed, paraffin-embedded anterior segments. Retinal ganglion cells (RGCs) were quantified on retrograde and Brn-3a-labeled flat mounts using MetaMorph software.
BMP2-treated cells displayed marked increase in calcification. Trabecular meshwork tissue showed moderate ALP activity at 13 days postinjection. Fifty-four of 55 BN and 15 of 19 Wistar rats displayed significantly elevated IOP. In a representative 29-day experiment, the integral IOP difference between treated and control eyes was 367.7 ± 83 mm Hg-days (P = 0.007). Morphological evaluation revealed a well-organized trabecular meshwork tissue, exhibiting denser matrix in the treated eyes. The Ad5BMP2-treated eye showed 34.4% ± 4.8% (P = 0.00002) loss of peripheral RGC over controls.
Gene transfer of the calcification inducer BMP2 gene to the trabecular meshwork induces elevated IOP in living rats without altering the basic structure of the tissue. This strategy generates an elevated IOP model in rats that would be useful for evaluation of glaucoma drugs targeting the outflow pathway. |
| doi_str_mv | 10.1167/iovs.13-11651 |
| format | Article |
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Calcification was assessed by alizarin red staining in primary human trabecular meshwork (HTM) cells and alkaline phosphatase (ALP) activity in the angle tissue. Brown Norway (BN) and Wistar rats were intracamerally injected with Ad5BMP2 (OS) and control Ad5.CMV-Null (OD). IOPs were taken twice a week and expressed as mean integral pressures. Morphology was assessed on fixed, paraffin-embedded anterior segments. Retinal ganglion cells (RGCs) were quantified on retrograde and Brn-3a-labeled flat mounts using MetaMorph software.
BMP2-treated cells displayed marked increase in calcification. Trabecular meshwork tissue showed moderate ALP activity at 13 days postinjection. Fifty-four of 55 BN and 15 of 19 Wistar rats displayed significantly elevated IOP. In a representative 29-day experiment, the integral IOP difference between treated and control eyes was 367.7 ± 83 mm Hg-days (P = 0.007). Morphological evaluation revealed a well-organized trabecular meshwork tissue, exhibiting denser matrix in the treated eyes. The Ad5BMP2-treated eye showed 34.4% ± 4.8% (P = 0.00002) loss of peripheral RGC over controls.
Gene transfer of the calcification inducer BMP2 gene to the trabecular meshwork induces elevated IOP in living rats without altering the basic structure of the tissue. This strategy generates an elevated IOP model in rats that would be useful for evaluation of glaucoma drugs targeting the outflow pathway.</description><identifier>ISSN: 1552-5783</identifier><identifier>ISSN: 0146-0404</identifier><identifier>EISSN: 1552-5783</identifier><identifier>DOI: 10.1167/iovs.13-11651</identifier><identifier>PMID: 23821199</identifier><language>eng</language><publisher>United States: The Association for Research in Vision and Ophthalmology</publisher><subject>Adolescent ; Adult ; Animals ; Bone Morphogenetic Protein 2 - administration & dosage ; Bone Morphogenetic Protein 2 - biosynthesis ; Bone Morphogenetic Protein 2 - genetics ; Calcinosis - genetics ; Calcinosis - metabolism ; Calcinosis - pathology ; Cells, Cultured ; Disease Models, Animal ; Gene Expression Regulation ; Gene Transfer Techniques ; Humans ; Immunohistochemistry ; Intraocular Pressure - physiology ; Male ; Ocular Hypertension - genetics ; Ocular Hypertension - metabolism ; Ocular Hypertension - physiopathology ; Rats ; Rats, Inbred BN ; Rats, Wistar ; Real-Time Polymerase Chain Reaction ; RNA - genetics ; Trabecular Meshwork - drug effects ; Trabecular Meshwork - pathology ; Young Adult</subject><ispartof>Investigative ophthalmology & visual science, 2013-08, Vol.54 (8), p.5441-5455</ispartof><rights>Copyright 2013 The Association for Research in Vision and Ophthalmology, Inc. 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c387t-1681cadfd1beb29ca2725388aff0274a48f4b2ab3c8faf54425f0313c1698ad33</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3743456/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3743456/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23821199$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Buie, Lakisha K</creatorcontrib><creatorcontrib>Karim, Md Zahidul</creatorcontrib><creatorcontrib>Smith, Matthew H</creatorcontrib><creatorcontrib>Borrás, Teresa</creatorcontrib><title>Development of a model of elevated intraocular pressure in rats by gene transfer of bone morphogenetic protein 2</title><title>Investigative ophthalmology & visual science</title><addtitle>Invest Ophthalmol Vis Sci</addtitle><description>To determine whether inducing calcification in the trabecular meshwork results in elevated IOP in living rats. To use this property to create an elevated IOP animal model by gene transfer of bone morphogenetic protein 2 (BMP2).
Calcification was assessed by alizarin red staining in primary human trabecular meshwork (HTM) cells and alkaline phosphatase (ALP) activity in the angle tissue. Brown Norway (BN) and Wistar rats were intracamerally injected with Ad5BMP2 (OS) and control Ad5.CMV-Null (OD). IOPs were taken twice a week and expressed as mean integral pressures. Morphology was assessed on fixed, paraffin-embedded anterior segments. Retinal ganglion cells (RGCs) were quantified on retrograde and Brn-3a-labeled flat mounts using MetaMorph software.
BMP2-treated cells displayed marked increase in calcification. Trabecular meshwork tissue showed moderate ALP activity at 13 days postinjection. Fifty-four of 55 BN and 15 of 19 Wistar rats displayed significantly elevated IOP. In a representative 29-day experiment, the integral IOP difference between treated and control eyes was 367.7 ± 83 mm Hg-days (P = 0.007). Morphological evaluation revealed a well-organized trabecular meshwork tissue, exhibiting denser matrix in the treated eyes. The Ad5BMP2-treated eye showed 34.4% ± 4.8% (P = 0.00002) loss of peripheral RGC over controls.
Gene transfer of the calcification inducer BMP2 gene to the trabecular meshwork induces elevated IOP in living rats without altering the basic structure of the tissue. This strategy generates an elevated IOP model in rats that would be useful for evaluation of glaucoma drugs targeting the outflow pathway.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Animals</subject><subject>Bone Morphogenetic Protein 2 - administration & dosage</subject><subject>Bone Morphogenetic Protein 2 - biosynthesis</subject><subject>Bone Morphogenetic Protein 2 - genetics</subject><subject>Calcinosis - genetics</subject><subject>Calcinosis - metabolism</subject><subject>Calcinosis - pathology</subject><subject>Cells, Cultured</subject><subject>Disease Models, Animal</subject><subject>Gene Expression Regulation</subject><subject>Gene Transfer Techniques</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Intraocular Pressure - physiology</subject><subject>Male</subject><subject>Ocular Hypertension - genetics</subject><subject>Ocular Hypertension - metabolism</subject><subject>Ocular Hypertension - physiopathology</subject><subject>Rats</subject><subject>Rats, Inbred BN</subject><subject>Rats, Wistar</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>RNA - genetics</subject><subject>Trabecular Meshwork - drug effects</subject><subject>Trabecular Meshwork - pathology</subject><subject>Young Adult</subject><issn>1552-5783</issn><issn>0146-0404</issn><issn>1552-5783</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUctOwzAQtBCIlsKRK_KRS0r8atwLEipPqRIXOFuOs26DkjjYSaX-PQ4tVTnt7O7MrK1B6JqkU0Jm2V3pNmFKWBIbQU7QmAhBE5FJdnqER-gihK80pYTQ9ByNKJMRzudj1D7CBirX1tB02Fmsce0KqAYIFWx0BwUum85rZ_pKe9x6CKH3EIfY6y7gfItX0ACOlCZY8IMyd3FQO9-u3bDrShN1roOooZfozOoqwNW-TtDn89PH4jVZvr-8LR6WiWEy6xIyk8TowhYkh5zOjaYZFUxKbW1KM665tDynOmdGWm0F51TYlBFmyGwudcHYBN3vfNs-r6EwMHyiUq0va-23yulS_d805Vqt3EaxjDMuZtHgdm_g3XcPoVN1GQxUlW7A9UERTjmjlIs0UpMd1XgXggd7OENSNaSkhpQUYeo3pci_OX7bgf0XC_sB-tWRRw</recordid><startdate>20130813</startdate><enddate>20130813</enddate><creator>Buie, Lakisha K</creator><creator>Karim, Md Zahidul</creator><creator>Smith, Matthew H</creator><creator>Borrás, Teresa</creator><general>The Association for Research in Vision and Ophthalmology</general><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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20130813</creationdate><title>Development of a model of elevated intraocular pressure in rats by gene transfer of bone morphogenetic protein 2</title><author>Buie, Lakisha K ; Karim, Md Zahidul ; Smith, Matthew H ; Borrás, Teresa</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c387t-1681cadfd1beb29ca2725388aff0274a48f4b2ab3c8faf54425f0313c1698ad33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Animals</topic><topic>Bone Morphogenetic Protein 2 - administration & dosage</topic><topic>Bone Morphogenetic Protein 2 - biosynthesis</topic><topic>Bone Morphogenetic Protein 2 - genetics</topic><topic>Calcinosis - genetics</topic><topic>Calcinosis - metabolism</topic><topic>Calcinosis - pathology</topic><topic>Cells, Cultured</topic><topic>Disease Models, Animal</topic><topic>Gene Expression Regulation</topic><topic>Gene Transfer Techniques</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Intraocular Pressure - physiology</topic><topic>Male</topic><topic>Ocular Hypertension - genetics</topic><topic>Ocular Hypertension - metabolism</topic><topic>Ocular Hypertension - physiopathology</topic><topic>Rats</topic><topic>Rats, Inbred BN</topic><topic>Rats, Wistar</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>RNA - genetics</topic><topic>Trabecular Meshwork - drug effects</topic><topic>Trabecular Meshwork - pathology</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Buie, Lakisha K</creatorcontrib><creatorcontrib>Karim, Md Zahidul</creatorcontrib><creatorcontrib>Smith, Matthew H</creatorcontrib><creatorcontrib>Borrás, Teresa</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Investigative ophthalmology & visual science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Buie, Lakisha K</au><au>Karim, Md Zahidul</au><au>Smith, Matthew H</au><au>Borrás, Teresa</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Development of a model of elevated intraocular pressure in rats by gene transfer of bone morphogenetic protein 2</atitle><jtitle>Investigative ophthalmology & visual science</jtitle><addtitle>Invest Ophthalmol Vis Sci</addtitle><date>2013-08-13</date><risdate>2013</risdate><volume>54</volume><issue>8</issue><spage>5441</spage><epage>5455</epage><pages>5441-5455</pages><issn>1552-5783</issn><issn>0146-0404</issn><eissn>1552-5783</eissn><abstract>To determine whether inducing calcification in the trabecular meshwork results in elevated IOP in living rats. To use this property to create an elevated IOP animal model by gene transfer of bone morphogenetic protein 2 (BMP2).
Calcification was assessed by alizarin red staining in primary human trabecular meshwork (HTM) cells and alkaline phosphatase (ALP) activity in the angle tissue. Brown Norway (BN) and Wistar rats were intracamerally injected with Ad5BMP2 (OS) and control Ad5.CMV-Null (OD). IOPs were taken twice a week and expressed as mean integral pressures. Morphology was assessed on fixed, paraffin-embedded anterior segments. Retinal ganglion cells (RGCs) were quantified on retrograde and Brn-3a-labeled flat mounts using MetaMorph software.
BMP2-treated cells displayed marked increase in calcification. Trabecular meshwork tissue showed moderate ALP activity at 13 days postinjection. Fifty-four of 55 BN and 15 of 19 Wistar rats displayed significantly elevated IOP. In a representative 29-day experiment, the integral IOP difference between treated and control eyes was 367.7 ± 83 mm Hg-days (P = 0.007). Morphological evaluation revealed a well-organized trabecular meshwork tissue, exhibiting denser matrix in the treated eyes. The Ad5BMP2-treated eye showed 34.4% ± 4.8% (P = 0.00002) loss of peripheral RGC over controls.
Gene transfer of the calcification inducer BMP2 gene to the trabecular meshwork induces elevated IOP in living rats without altering the basic structure of the tissue. This strategy generates an elevated IOP model in rats that would be useful for evaluation of glaucoma drugs targeting the outflow pathway.</abstract><cop>United States</cop><pub>The Association for Research in Vision and Ophthalmology</pub><pmid>23821199</pmid><doi>10.1167/iovs.13-11651</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Adolescent Adult Animals Bone Morphogenetic Protein 2 - administration & dosage Bone Morphogenetic Protein 2 - biosynthesis Bone Morphogenetic Protein 2 - genetics Calcinosis - genetics Calcinosis - metabolism Calcinosis - pathology Cells, Cultured Disease Models, Animal Gene Expression Regulation Gene Transfer Techniques Humans Immunohistochemistry Intraocular Pressure - physiology Male Ocular Hypertension - genetics Ocular Hypertension - metabolism Ocular Hypertension - physiopathology Rats Rats, Inbred BN Rats, Wistar Real-Time Polymerase Chain Reaction RNA - genetics Trabecular Meshwork - drug effects Trabecular Meshwork - pathology Young Adult |
| title | Development of a model of elevated intraocular pressure in rats by gene transfer of bone morphogenetic protein 2 |
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