Absence of a secondary glucocorticoid response in C57BL/6J mice treated with topical dexamethasone.
Glucocorticoids such as dexamethasone can cause an increase in intraocular pressure (IOP) in some of the population, but not all. In this paper we used a mouse model of glucocorticoid induced ocular hypertension to examine the changes in the anterior segment of the eye in mice that failed to respond...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2018-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5834162?pdf=render |
| _version_ | 1819240003350298624 |
|---|---|
| author | Jennifer A Faralli Kaylee D Dimeo Ralph M Trane Donna Peters |
| author_facet | Jennifer A Faralli Kaylee D Dimeo Ralph M Trane Donna Peters |
| author_sort | Jennifer A Faralli |
| collection | DOAJ |
| description | Glucocorticoids such as dexamethasone can cause an increase in intraocular pressure (IOP) in some of the population, but not all. In this paper we used a mouse model of glucocorticoid induced ocular hypertension to examine the changes in the anterior segment of the eye in mice that failed to respond to glucocorticoid treatment with a sustained increase in IOP. C57BL/6J mice were treated with either 0.1% dexamethasone sodium phosphate ophthalmic solution or sterile PBS 3 times daily for up to 5 weeks. IOP was measured weekly at approximately the same time of the day. After 3-5 weeks of treatment, eyes were enucleated and evaluated for changes associated with steroid induced glaucoma. These studies showed that IOP was significantly elevated in dexamethasone (DEX) treated mice compared to PBS treated mice after 3 weeks of treatment, but IOP in DEX treated mice returned to baseline levels after 5 weeks of treatment. All the mice demonstrated a response to the glucocorticoid treatments and showed an elevation in FKBP5 expression after both 3 and 5 weeks of DEX treatment (primary glucocorticoid response protein) and a weight loss. Western blot analysis of anterior segments from treated mice, however, did not show an increase in secondary glucocorticoid response proteins such as β3 integrin or myocilin. Fibronectin levels were also not statistically different. The data suggest that in mice, which do not exhibit a prolonged increase in IOP in response to the DEX treatment, there is a compensatory mechanism that can prevent or turn off the secondary glucocorticoid response. |
| first_indexed | 2024-12-23T14:01:06Z |
| format | Article |
| id | doaj.art-c6b15b1473f24488b2b030a6d720d77e |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T14:01:06Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-c6b15b1473f24488b2b030a6d720d77e2022-12-21T17:44:19ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01133e019266510.1371/journal.pone.0192665Absence of a secondary glucocorticoid response in C57BL/6J mice treated with topical dexamethasone.Jennifer A FaralliKaylee D DimeoRalph M TraneDonna PetersGlucocorticoids such as dexamethasone can cause an increase in intraocular pressure (IOP) in some of the population, but not all. In this paper we used a mouse model of glucocorticoid induced ocular hypertension to examine the changes in the anterior segment of the eye in mice that failed to respond to glucocorticoid treatment with a sustained increase in IOP. C57BL/6J mice were treated with either 0.1% dexamethasone sodium phosphate ophthalmic solution or sterile PBS 3 times daily for up to 5 weeks. IOP was measured weekly at approximately the same time of the day. After 3-5 weeks of treatment, eyes were enucleated and evaluated for changes associated with steroid induced glaucoma. These studies showed that IOP was significantly elevated in dexamethasone (DEX) treated mice compared to PBS treated mice after 3 weeks of treatment, but IOP in DEX treated mice returned to baseline levels after 5 weeks of treatment. All the mice demonstrated a response to the glucocorticoid treatments and showed an elevation in FKBP5 expression after both 3 and 5 weeks of DEX treatment (primary glucocorticoid response protein) and a weight loss. Western blot analysis of anterior segments from treated mice, however, did not show an increase in secondary glucocorticoid response proteins such as β3 integrin or myocilin. Fibronectin levels were also not statistically different. The data suggest that in mice, which do not exhibit a prolonged increase in IOP in response to the DEX treatment, there is a compensatory mechanism that can prevent or turn off the secondary glucocorticoid response.http://europepmc.org/articles/PMC5834162?pdf=render |
| spellingShingle | Jennifer A Faralli Kaylee D Dimeo Ralph M Trane Donna Peters Absence of a secondary glucocorticoid response in C57BL/6J mice treated with topical dexamethasone. PLoS ONE |
| title | Absence of a secondary glucocorticoid response in C57BL/6J mice treated with topical dexamethasone. |
| title_full | Absence of a secondary glucocorticoid response in C57BL/6J mice treated with topical dexamethasone. |
| title_fullStr | Absence of a secondary glucocorticoid response in C57BL/6J mice treated with topical dexamethasone. |
| title_full_unstemmed | Absence of a secondary glucocorticoid response in C57BL/6J mice treated with topical dexamethasone. |
| title_short | Absence of a secondary glucocorticoid response in C57BL/6J mice treated with topical dexamethasone. |
| title_sort | absence of a secondary glucocorticoid response in c57bl 6j mice treated with topical dexamethasone |
| url | http://europepmc.org/articles/PMC5834162?pdf=render |
| work_keys_str_mv | AT jenniferafaralli absenceofasecondaryglucocorticoidresponseinc57bl6jmicetreatedwithtopicaldexamethasone AT kayleeddimeo absenceofasecondaryglucocorticoidresponseinc57bl6jmicetreatedwithtopicaldexamethasone AT ralphmtrane absenceofasecondaryglucocorticoidresponseinc57bl6jmicetreatedwithtopicaldexamethasone AT donnapeters absenceofasecondaryglucocorticoidresponseinc57bl6jmicetreatedwithtopicaldexamethasone |