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Published on: January 25, 2019
ProMMP-9 (92 kDa gelatinase) in vitreous fluid of patients with proliferative diabetic retinopathy
1Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan. h-kosano@pharm.teikyo-u.ac.jp
Abstract:
Matrix metalloproteinases (MMPs) are implicated in tissue destruction during various pathophysiologic conditions. The vitreous body is a gel-like extracellular matrix that undergoes liquefaction during aging and pathological processes. To investigate the pathogenic role of MMPs in proliferative diabetic retinopathy (PDR), we studied 73 eyes from PDR patients and 25 eyes from patients with non-diabetic ocular diseases. Vitreous MMPs were measured by zymography. Retinopathy was assessed by ophthalmoscopy and PDR was classified into 3 stages, 'naked', 'active', and 'quiescent'. Although proMMP-9 was expressed in only 8% (2/25) of non-diabetic patients, it was expressed in more than 80% (38/47) of 'active' PDR patients and still expressed in 60% (9/15) of those with 'quiescent' PDR. Vascular endothelial growth factor (VEGF) in vitreous fluids was undetectable (<0.16 ng/ml) in most of the non-diabetic patients, and was maximally elevated in the 'active' PDR patients (mean=2.20 ng/ml, range; 0.16-7.61), declining in patients with 'quiescent' PDR (1.04 ng/ml, 0.16-3.77). These results suggest that MMP-9 is one of the noteworthy factors in relation to the progress of PDR, as well as angiogenic cytokines such as VEGF.
Insights
Matrix metalloproteinases (MMPs), specifically MMP-9, are significantly elevated in proliferative diabetic retinopathy (PDR). This suggests MMP-9 plays a key role in PDR progression alongside vascular endothelial growth factor (VEGF).
Area of Science:
- Ophthalmology
- Molecular Biology
- Biochemistry
Background:
- Matrix metalloproteinases (MMPs) contribute to tissue degradation in various diseases.
- Vitreous liquefaction occurs with aging and in pathological eye conditions.
- Proliferative diabetic retinopathy (PDR) involves complex ocular changes.
Purpose of the Study:
- To investigate the role of MMPs, particularly MMP-9, in the pathogenesis of PDR.
- To correlate MMP levels with PDR staging and vascular endothelial growth factor (VEGF) levels.
Main Methods:
- Vitreous samples were collected from PDR patients (73 eyes) and non-diabetic controls (25 eyes).
- Matrix metalloproteinases (MMPs) in vitreous fluid were quantified using zymography.
- Retinopathy severity was assessed, and PDR was staged into 'naked', 'active', and 'quiescent' categories.
Main Results:
- ProMMP-9 expression was found in over 80% of 'active' PDR patients, compared to only 8% in non-diabetics.
- Elevated proMMP-9 levels persisted in 60% of 'quiescent' PDR patients.
- Vascular endothelial growth factor (VEGF) levels were highest in 'active' PDR and decreased in 'quiescent' PDR, correlating with MMP-9 presence.
Conclusions:
- MMP-9 is a significant factor in the progression of proliferative diabetic retinopathy (PDR).
- MMP-9 may act in concert with angiogenic factors like VEGF in PDR pathogenesis.
- These findings highlight MMP-9 as a potential therapeutic target in PDR management.
