Vitreous and aqueous concentrations of proangiogenic, antiangiogenic factors and other cytokines in diabetic retinopathy patients with macular edema: Implications for structural differences in macular profiles

Patel, Jawaharlal M.; Tombran-Tink, Joyce; Hykin, Phil; Gregor, Zdeněk; Cree, Ian A.

doi:10.1016/j.exer.2005.10.002

Cited by 128 publications

(88 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…PEDF alterations in patients with PDR compared with nondiabetic patients are controversial. Some previous studies pointed to reductions in the levels of vitreous PEDF in patients suffering from PDR [6,18-20]. Conversely, elevated levels of PEDF were detected in some studies [13,21].…”

Section: Discussionmentioning

confidence: 95%

Characterisation of the vitreous proteome in proliferative diabetic retinopathy

Wang

Hu³

et al. 2012

Proteome Sci

View full text Add to dashboard Cite

BackgroundDiabetes can lead to serious microvascular complications such as proliferative diabetic retinopathy (PDR), which results in severe vision loss. The diabetes-induced alterations in the vitreous protein composition in diabetic patients with PDR may be responsible for the presence of PDR. The vitreous humour can be utilised in a variety of studies aimed toward the discovery of new targets for the treatment or prevention of PDR and the identification of novel disease mechanisms. The aim of this study was to compare the protein profile of vitreous humour from diabetic patients with PDR with that of vitreous humour from normal human eyes donated for corneal transplant.ResultsVitreous humour from type 2 diabetic patients with PDR (n = 10) and from normal human eyes donated for corneal transplant (n = 10) were studied. The comparative proteomic analysis was performed using two-dimensional fluorescence difference gel electrophoresis (2-D DIGE). Differentially produced proteins (abundance ratio > 2 or < -2, p < 0.01) were identified by matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS) and MALDI-TOF tandem mass spectrometry. A total of 1242 protein spots were detected on the 2-D master gel of the samples, and 57 spots that exhibited statistically significant variations were successfully identified. The spots corresponded to peptide fragments of 29 proteins, including 8 proteins that increased and 21 proteins that decreased in PDR. Excluding the serum proteins from minor vitreous haemorrhage, 19 proteins were found to be differentially produced in PDR patients compared with normal subjects; 6 of these proteins have never been reported to be differentially expressed in PDR vitreous: N(G),N(G)-dimethylarginine dimethylaminohydrolase 1 (DDAH 1), tubulin alpha-1B chain, gamma-enolase, cytosolic acyl coenzyme A thioester hydrolase, malate dehydrogenase and phosphatidylethanolamine-binding protein 1 (PEBP 1). The differential production of pigment epithelium-derived factor (PEDF) and clusterin was confirmed by Western blot analysis.ConclusionsThese data provide an in-depth analysis of the human vitreous proteome and reveal protein alterations that are possibly involved in the pathogenesis of PDR. Further investigation of these special proteins may provide potential new targets for the treatment or the prevention of PDR.

show abstract

Section: Discussionmentioning

confidence: 95%

Characterisation of the vitreous proteome in proliferative diabetic retinopathy

Wang

Hu³

et al. 2012

Proteome Sci

View full text Add to dashboard Cite

show abstract

“…[1][2][3][4][5][6][7] Vascular endothelial growth factor (VEGF), which is also a proangiogenic factor, is the best known of these factors. High concentrations of this peptide have been found in the vitreous of patients with macular oedema secondary to several diseases.…”

Section: Introductionmentioning

confidence: 99%

Vitreous levels of erythropoietin in patients with macular oedema secondary to retinal vein occlusions: a comparative study with diabetic macular oedema

Garcí-Arumí

Fonollosa

Macia

et al. 2008

Eye

View full text Add to dashboard Cite

Objective In a recent study, we found high levels of erythropoietin (EPO) in patients with diabetic macular oedema (DME), suggesting a role of EPO in the pathogenesis of this condition. To investigate a possible relationship between EPO and other diseases causing macular oedema, we determined vitreous levels of this peptide in patients with macular oedema secondary to retinal vein occlusion (RVO) and compared them with levels in patients with DME and control patients. Methods Vitreous and serum samples were obtained from patients with macular oedema secondary to RVO, DME, epiretinal membrane, and macular hole (controls). EPO was measured by radioimmunoassay. Results No differences were found in median vitreous EPO levels between patients with RVO and controls: RVO, 76 mU/ml (30-806) vs controls, 25 mU/ml (10-75) (P ¼ 0.105). Median EPO concentration was higher in DME patients than in patients with RVO or controls: DME, 430 mU/ml (41-3000) vs RVO, 76 mU/ml (30-806) (Po0.0001) vs controls, 25 mU/ml (10-75) (Po0.0001). Conclusions EPO levels are not elevated in patients with macular oedema secondary to RVO. Patients with DME have high levels of EPO. These results suggest that EPO could be involved in the pathogenesis of diabetic retinopathy, but not in macular oedema secondary to RVO.

show abstract

“…To date, biochemical studies of human diabetic retinopathy have been mostly limited to analysis of the vitreous [22,[24][25][26]. These analyses have revealed several pathways and factors that provided insight into diabetes-related ocular alterations.…”

Section: Resultsmentioning

confidence: 99%

Human retinal pigment epithelium proteome changes in early diabetes

et al. 2008

View full text Add to dashboard Cite

Aims/hypothesis Diabetic retinopathy is the most common complication of diabetes and a leading cause of blindness among working-age adults. Anatomical and functional changes occur in the retina and retinal pigment epithelium (RPE) prior to clinical symptoms of the disease. However, the molecular mechanisms responsible for these early changes, particularly in the RPE, remain unclear. To begin defining the molecular changes associated with pre-retinopathic diabetes, we conducted a comparative proteomics study of human donor RPE. Methods The RPE was dissected from diabetic human donor eyes with no clinically apparent diabetic retinopathy (n=6) and from eyes of age-matched control donors (n= 17). Soluble proteins were separated based upon their mass and charge using two-dimensional (2-D) gel electrophoresis. Protein spots were visualised with a fluorescent dye and spot densities were compared between diabetic and control gels. Proteins from spots with significant disease-related changes in density were identified using mass spectrometry.Results Analysis of 325 spots on 2-D gels identified 31 spots that were either up-or downregulated relative to those from age-matched control donors. The protein identity of 18 spots was determined by mass spectrometry. A majority of altered proteins belonged to two major functional groups, metabolism and chaperones, while other affected categories included protein degradation, synthesis and transport, oxidoreductases, cytoskeletal structure and retinoid metabolism. Conclusions/interpretation Changes identified in the RPE proteome of pre-retinopathic diabetic donor eyes compared with age-matched controls suggest specific cellular alterations that may contribute to diabetic retinopathy. Defining the pre-retinopathic changes affecting the RPE could provide important insight into the molecular events that lead to this disease.

show abstract

Vitreous and aqueous concentrations of proangiogenic, antiangiogenic factors and other cytokines in diabetic retinopathy patients with macular edema: Implications for structural differences in macular profiles

Cited by 128 publications

References 26 publications

Characterisation of the vitreous proteome in proliferative diabetic retinopathy

Characterisation of the vitreous proteome in proliferative diabetic retinopathy

Vitreous levels of erythropoietin in patients with macular oedema secondary to retinal vein occlusions: a comparative study with diabetic macular oedema

Human retinal pigment epithelium proteome changes in early diabetes

Contact Info

Product

Resources

About