Ocular expression of cyclin-dependent kinase 5 in patients with proliferative diabetic retinopathy
Hiroki Sano1,2, Kazuhiko Namekata2, Masanori Niki1
1Department of Ophthalmology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Aims/Introduction:
Inhibition of peroxisome proliferator-activated receptor gamma (PPARγ) phosphorylation mediated by cyclin-dependent kinase 5 (Cdk5) is one of the main mechanisms of action of antidiabetic drugs. In this study, we analyzed the ocular expression and activation of Cdk5 in patients with proliferative diabetic retinopathy (PDR).
Materials And Methods:
The concentrations of PPARγ, Cdk5 and its activating subunit (p35) were determined in the vitreous body of 24 PDR and 63 control eyes by enzyme-linked immunosorbent assay. In addition, the messenger ribonucleic acid and protein expression levels of PPARγ, Cdk5 and p35 were measured in proliferative neovascular membranes from seven PDR eyes and non-neovascular epiretinal membranes from five control eyes by quantitative real-time polymerase chain reaction and immunohistochemical analysis.
Results:
PPARγ, Cdk5 and p35 concentrations in the vitreous body were significantly higher in the PDR group compared with the control group. There was also a positive significant correlation of Cdk5 with PPARγ and p35 in the PDR group. Furthermore, the messenger ribonucleic acid expression levels of PPARγ, Cdk5 and p35 in proliferative neovascular membranes were significantly higher in the PDR group compared with the control group. Immunostaining showed increased protein expression levels of PPARγ, Cdk5 and p35 in proliferative neovascular membranes in the PDR group compared with the control group.
Conclusions:
Cdk5 activation is involved in PDR pathogenesis through PPARγ expression, and inhibition of Cdk5-mediated PPARγ phosphorylation might be a new therapeutic target for treatment of PDR.
Insights
Cyclin-dependent kinase 5 (Cdk5) activation is implicated in proliferative diabetic retinopathy (PDR) through peroxisome proliferator-activated receptor gamma (PPARγ) expression. Inhibiting Cdk5-mediated PPARγ phosphorylation may offer a novel therapeutic strategy for PDR.
Area of Science:
- Ophthalmology
- Endocrinology
- Molecular Biology
Background:
- Diabetic retinopathy (DR) is a leading cause of vision loss.
- Cyclin-dependent kinase 5 (Cdk5) regulates peroxisome proliferator-activated receptor gamma (PPARγ) phosphorylation, a mechanism relevant to antidiabetic drug action.
- The role of Cdk5 in the ocular tissues of proliferative diabetic retinopathy (PDR) remains to be fully elucidated.
Purpose of the Study:
- To investigate the expression and activation of Cdk5 in the ocular tissues of patients with PDR.
- To explore the relationship between Cdk5, its activator p35, and PPARγ in PDR pathogenesis.
Main Methods:
- Enzyme-linked immunosorbent assay (ELISA) was used to quantify PPARγ, Cdk5, and p35 concentrations in the vitreous humor of PDR and control eyes.
- Quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical analysis were performed to assess messenger ribonucleic acid (mRNA) and protein expression levels in neovascular membranes.
Main Results:
- Significantly elevated concentrations of PPARγ, Cdk5, and p35 were observed in the vitreous of PDR patients compared to controls.
- Positive correlations were found between Cdk5 and both PPARγ and p35 in the PDR group.
- Elevated mRNA and protein expression of PPARγ, Cdk5, and p35 were detected in neovascular membranes from PDR eyes.
Conclusions:
- Cdk5 activation plays a role in PDR development, potentially via its influence on PPARγ expression.
- Targeting Cdk5-mediated PPARγ phosphorylation presents a potential new therapeutic avenue for PDR treatment.
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