Ocular TGF-β, Matrix Metalloproteinases, and TIMP-1 Increase with the Development and Progression of Diabetic Retinopathy in Type 2 Diabetes Mellitus
Diabetic retinopathy (DR) is a sight-threatening late complication of diabetes mellitus (DM). Even though its pathophysiology has not been fully elucidated, several studies suggested a role for transforming growth factor- (TGF-) β, matrix metalloproteinases (MMPs), and tissue inhibitors of matrix me...
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| Format: | Article |
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2021-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2021/9811361 |
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| author | Lucia Saucedo Isabel B. Pfister Souska Zandi Christin Gerhardt Justus G. Garweg |
| author_facet | Lucia Saucedo Isabel B. Pfister Souska Zandi Christin Gerhardt Justus G. Garweg |
| author_sort | Lucia Saucedo |
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| description | Diabetic retinopathy (DR) is a sight-threatening late complication of diabetes mellitus (DM). Even though its pathophysiology has not been fully elucidated, several studies suggested a role for transforming growth factor- (TGF-) β, matrix metalloproteinases (MMPs), and tissue inhibitors of matrix metalloproteinase (TIMP) in the onset and progression of the disease. Consequently, the aim of this study was to analyze the concentrations of TGF-β1, TGF-β2, TGF-β3, MMP-3, MMP-9, and TIMP-1 in patients with different stages of DR in order to identify stage-specific changes in their concentrations during the progression of the disease. Serum and aqueous humor (AH) samples were collected during intraocular surgery, and eyes were classified into the following groups: healthy controls (n=17), diabetic patients with non-apparent DR (n=23), mild/moderate nonproliferative DR (NPDR) (n=13), and advanced NPDR/proliferative DR (PDR) without vitreal hemorrhage (n=14). None of the patients had been under anti-VEGF or laser treatment within six months prior to surgery. In the AH, TGF-β1 levels increased in advanced NPDR/PDR by a factor of 5.5 compared to the control group. Similarly, an increase in MMP-3 and TIMP-1 levels in the AH was evident in the later stages of DR, corresponding to a 7.7- and 2.4-fold increase compared to the control group, respectively, whereas serum levels of the studied proteins remained similar. In conclusion, increased concentrations of TGF-β1, MMP-3, and TIMP-1 in the AH, but not in the serum, in advanced NPDR/PDR indicate that the intraocular regulation for these cytokines is independent of the systemic one and suggest their involvement in the progression of DR. |
| format | Article |
| id | doaj-art-ad2d6c96ea8f4662a1cc6cc540c714b9 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
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| series | Mediators of Inflammation |
| spelling | doaj-art-ad2d6c96ea8f4662a1cc6cc540c714b92025-02-03T07:23:32ZengWileyMediators of Inflammation0962-93511466-18612021-01-01202110.1155/2021/98113619811361Ocular TGF-β, Matrix Metalloproteinases, and TIMP-1 Increase with the Development and Progression of Diabetic Retinopathy in Type 2 Diabetes MellitusLucia Saucedo0Isabel B. Pfister1Souska Zandi2Christin Gerhardt3Justus G. Garweg4Swiss Eye Institute, Rotkreuz and Retina Clinic, Berner Augenklinik am Lindenhofspital, 3012, SwitzerlandSwiss Eye Institute, Rotkreuz and Retina Clinic, Berner Augenklinik am Lindenhofspital, 3012, SwitzerlandSwiss Eye Institute, Rotkreuz and Retina Clinic, Berner Augenklinik am Lindenhofspital, 3012, SwitzerlandSwiss Eye Institute, Rotkreuz and Retina Clinic, Berner Augenklinik am Lindenhofspital, 3012, SwitzerlandSwiss Eye Institute, Rotkreuz and Retina Clinic, Berner Augenklinik am Lindenhofspital, 3012, SwitzerlandDiabetic retinopathy (DR) is a sight-threatening late complication of diabetes mellitus (DM). Even though its pathophysiology has not been fully elucidated, several studies suggested a role for transforming growth factor- (TGF-) β, matrix metalloproteinases (MMPs), and tissue inhibitors of matrix metalloproteinase (TIMP) in the onset and progression of the disease. Consequently, the aim of this study was to analyze the concentrations of TGF-β1, TGF-β2, TGF-β3, MMP-3, MMP-9, and TIMP-1 in patients with different stages of DR in order to identify stage-specific changes in their concentrations during the progression of the disease. Serum and aqueous humor (AH) samples were collected during intraocular surgery, and eyes were classified into the following groups: healthy controls (n=17), diabetic patients with non-apparent DR (n=23), mild/moderate nonproliferative DR (NPDR) (n=13), and advanced NPDR/proliferative DR (PDR) without vitreal hemorrhage (n=14). None of the patients had been under anti-VEGF or laser treatment within six months prior to surgery. In the AH, TGF-β1 levels increased in advanced NPDR/PDR by a factor of 5.5 compared to the control group. Similarly, an increase in MMP-3 and TIMP-1 levels in the AH was evident in the later stages of DR, corresponding to a 7.7- and 2.4-fold increase compared to the control group, respectively, whereas serum levels of the studied proteins remained similar. In conclusion, increased concentrations of TGF-β1, MMP-3, and TIMP-1 in the AH, but not in the serum, in advanced NPDR/PDR indicate that the intraocular regulation for these cytokines is independent of the systemic one and suggest their involvement in the progression of DR.http://dx.doi.org/10.1155/2021/9811361 |
| spellingShingle | Lucia Saucedo Isabel B. Pfister Souska Zandi Christin Gerhardt Justus G. Garweg Ocular TGF-β, Matrix Metalloproteinases, and TIMP-1 Increase with the Development and Progression of Diabetic Retinopathy in Type 2 Diabetes Mellitus Mediators of Inflammation |
| title | Ocular TGF-β, Matrix Metalloproteinases, and TIMP-1 Increase with the Development and Progression of Diabetic Retinopathy in Type 2 Diabetes Mellitus |
| title_full | Ocular TGF-β, Matrix Metalloproteinases, and TIMP-1 Increase with the Development and Progression of Diabetic Retinopathy in Type 2 Diabetes Mellitus |
| title_fullStr | Ocular TGF-β, Matrix Metalloproteinases, and TIMP-1 Increase with the Development and Progression of Diabetic Retinopathy in Type 2 Diabetes Mellitus |
| title_full_unstemmed | Ocular TGF-β, Matrix Metalloproteinases, and TIMP-1 Increase with the Development and Progression of Diabetic Retinopathy in Type 2 Diabetes Mellitus |
| title_short | Ocular TGF-β, Matrix Metalloproteinases, and TIMP-1 Increase with the Development and Progression of Diabetic Retinopathy in Type 2 Diabetes Mellitus |
| title_sort | ocular tgf β matrix metalloproteinases and timp 1 increase with the development and progression of diabetic retinopathy in type 2 diabetes mellitus |
| url | http://dx.doi.org/10.1155/2021/9811361 |
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