Article: Aldose reductase deficiency reduced vascular changes in neonatal mouse retina in oxygen-induced retinopathy
| Title | Aldose reductase deficiency reduced vascular changes in neonatal mouse retina in oxygen-induced retinopathy |
|---|---|
| Authors | Fu, ZJ Li, SY Kociok, N Wong, D Chung, SK Lo, ACY |
| Issue Date | 2012 |
| Publisher | Association for Research in Vision and Ophthalmology. The Journal's web site is located at http://www.iovs.org |
| Citation | Investigative Ophthalmology & Visual Science, 2012, v. 53 n. 9, p. 5698-5712 [How to Cite?] DOI: http://dx.doi.org/10.1167/iovs.12-10122 |
| Abstract | PURPOSE: Retinal neovascularization is the major pathologic process in many ocular diseases and is associated with oxidative stress. Deficiency of aldose reductase (AR), the first enzyme in the polyol pathway for glucose metabolism, has been shown to reduce oxidative stress and blood vessel leakage. The present study aimed to investigate the effect of AR deficiency on retinal neovascularization in a murine oxygen-induced retinopathy (OIR) model. METHODS: Seven-day-old wild-type (WT) and AR-deficient (AR(-/-)) mice were exposed to 75% oxygen for 5 days and then returned to room air. Vascular obliteration, neovascularization, and blood vessel leakage were analyzed and compared. Immunohistochemistry for AR, nitrotyrosine (NT), poly(ADP-ribose) (PAR), glial fibrillary acidic protein (GFAP), and Iba-1, as well as Western blots for vascular endothelial growth factor (VEGF), phospho-Erk (p-Erk), phospho-Akt (p-Akt), and phospho-IkappaB (p-IkappaB) were performed. RESULTS: Compared with WT OIR retinae, AR(-/-) OIR retinae displayed significantly smaller central retinal vaso-obliterated area, less neovascularization, and reduced blood vessel leakage. Significantly reduced oxidative stress and glial responses were also observed in AR(-/-) OIR retinae. Moreover, reduced microglial response in the avascular area but increased microglial responses in the neovascular area were found with AR deficiency. Furthermore, expression levels of VEGF, p-Erk, p-Akt, and p-IkappaB were significantly reduced in AR(-/-) OIR retinae. CONCLUSIONS: Our observations indicated that AR deficiency reduced retinal vascular changes in the mouse model of OIR, indicating that AR can be a potential therapeutic target in ischemia-induced retinopathy. |
| ISSN | 0146-0404 2011 Impact Factor: 3.597 2011 SCImago Journal Rankings: 0.320 |
| DOI | http://dx.doi.org/10.1167/iovs.12-10122 |
| dc.contributor.author | Fu, ZJ |
|---|---|
| dc.contributor.author | Li, SY |
| dc.contributor.author | Kociok, N |
| dc.contributor.author | Wong, D |
| dc.contributor.author | Chung, SK |
| dc.contributor.author | Lo, ACY |
| dc.date.accessioned | 2012-09-20T08:50:38Z |
| dc.date.available | 2012-09-20T08:50:38Z |
| dc.date.issued | 2012 |
| dc.description.abstract | PURPOSE: Retinal neovascularization is the major pathologic process in many ocular diseases and is associated with oxidative stress. Deficiency of aldose reductase (AR), the first enzyme in the polyol pathway for glucose metabolism, has been shown to reduce oxidative stress and blood vessel leakage. The present study aimed to investigate the effect of AR deficiency on retinal neovascularization in a murine oxygen-induced retinopathy (OIR) model. METHODS: Seven-day-old wild-type (WT) and AR-deficient (AR(-/-)) mice were exposed to 75% oxygen for 5 days and then returned to room air. Vascular obliteration, neovascularization, and blood vessel leakage were analyzed and compared. Immunohistochemistry for AR, nitrotyrosine (NT), poly(ADP-ribose) (PAR), glial fibrillary acidic protein (GFAP), and Iba-1, as well as Western blots for vascular endothelial growth factor (VEGF), phospho-Erk (p-Erk), phospho-Akt (p-Akt), and phospho-IkappaB (p-IkappaB) were performed. RESULTS: Compared with WT OIR retinae, AR(-/-) OIR retinae displayed significantly smaller central retinal vaso-obliterated area, less neovascularization, and reduced blood vessel leakage. Significantly reduced oxidative stress and glial responses were also observed in AR(-/-) OIR retinae. Moreover, reduced microglial response in the avascular area but increased microglial responses in the neovascular area were found with AR deficiency. Furthermore, expression levels of VEGF, p-Erk, p-Akt, and p-IkappaB were significantly reduced in AR(-/-) OIR retinae. CONCLUSIONS: Our observations indicated that AR deficiency reduced retinal vascular changes in the mouse model of OIR, indicating that AR can be a potential therapeutic target in ischemia-induced retinopathy. |
| dc.identifier.citation | Investigative Ophthalmology & Visual Science, 2012, v. 53 n. 9, p. 5698-5712 [How to Cite?] DOI: http://dx.doi.org/10.1167/iovs.12-10122 |
| dc.identifier.doi | http://dx.doi.org/10.1167/iovs.12-10122 |
| dc.identifier.epage | 5712 |
| dc.identifier.hkuros | 208513 |
| dc.identifier.issn | 0146-0404 2011 Impact Factor: 3.597 2011 SCImago Journal Rankings: 0.320 |
| dc.identifier.issue | 9 |
| dc.identifier.pmid | 22836764 |
| dc.identifier.spage | 5698 |
| dc.identifier.uri | http://hdl.handle.net/10722/166833 |
| dc.identifier.volume | 53 |
| dc.language | eng |
| dc.publisher | Association for Research in Vision and Ophthalmology. The Journal's web site is located at http://www.iovs.org |
| dc.publisher.place | United States |
| dc.relation.ispartof | Investigative Ophthalmology & Visual Science |
| dc.subject.mesh | Aldehyde Reductase - deficiency |
| dc.subject.mesh | Animals, Newborn |
| dc.subject.mesh | Disease Models, Animal |
| dc.subject.mesh | Retinal Neovascularization - enzymology - pathology - prevention and control |
| dc.subject.mesh | Retinopathy of Prematurity - enzymology - pathology - prevention and control |
| dc.title | Aldose reductase deficiency reduced vascular changes in neonatal mouse retina in oxygen-induced retinopathy |
| dc.type | Article |