Elevation of Apolipoprotein A-I and Apolipoprotein H Levels in the Vitreous Fluid and Overexpression in the Retina of Diabetic Patients

Abstract

Objectives: To determine levels of apolipoprotein (apo) A-I and apo H in the vitreous fluid of patients with proliferative diabetic retinopathy (PDR) and to examine whether apo A-I and apo H messenger RNA (mRNA) levels are overexpressed in the diabetic retina. Methods: Vitreous samples from 4 diabetic patients with PDR and 8 nondiabetic patients with macular hole were selected for proteomic analysis. Fourteen additional samples (7 from patients with PDR and 7 from patients with macular hole) were used for Western blot analysis. Fourteen postmortem eyes (7 from diabetic and 7 from nondiabetic donors) were used to perform quantitative real-time polymerase chain reaction analysis. Results: Intravitreous apo A-I and apo H levels were significantly higher in patients with PDR than in the control group. The apo A-I and apo H mRNA levels obtained from the retinas of diabetic donors were significantly higher than those obtained from nondiabetic donors. Retinal pigment epithelium was the main contributor to the differences. Conclusions: Levels of apo A-I and apo H are elevated in the vitreous fluid of diabetic patients with PDR. In addition, we provide the first evidence, to our knowledge, that a higher expression of apo A-I and apo H mRNAs exists in the diabetic retina. Clinical Relevance: The results of this study may be relevant to new treatment strategies aimed toward reducing the development of diabetic retinopathy.

Dyslipidemia and Diabetic Retinopathy

“…Simo et al studied vitreous samples from 4 diabetic patients with PDR and 8 nondiabetic patients with macular hole for proteomic analysis of ApoA1 and ApoH [54]. The authors found that intravitreous ApoA1 and ApoH levels were significantly higher in patients with PDR than in the control group.…”

Vitreous Proteomics and Diabetic Retinopathy

“…29 Apo A 1 is a potent scavenger of oxygen-reactive species, and may have a role in protecting retina from the oxidative stress due to diabetes. 30 Garcia-Ramirez et al identified several components of the complement factor (C4b, factor B, C3 and C9) in PDR vitreous. 31 These authors postulated that activation of the complement cascade leads to initiation and progression of thrombosis, leucostasis and apoptosis, causing the vascular lesions in diabetic retinopathy.…”

“…The levels of PEDF, a potent inhibitor of angiogenesis, have not been found to be consistent across different studies, some reporting it to be down-regulated 31 ; and others as up-regulated 27,29 in the PDR vitreous. Other proteins that have been found to be increased in abundance in the diabetic vitreous include apo H 30 , prostaglandin –D2 synthetase, plasma glutathione peroxidase, intra retinol binding protein, catalase, 32 enolase, 32 prostaglandin-H2 D isomerase, 33 serine protease inhibitor, 33 ankyrin repeat domain 15 protein, 33 angiotensiogen 27 , prothrombin 27 , antithrombin III 27 , Factor XII 27 and peroxiredoxin-1. 27 …”

Proteomic analysis of tears following acupuncture treatment for menopausal dry eye disease by two-dimensional nano-liquid chromatography coupled with tandem mass spectrometry

“…However, Apo A-I was recently found in the vitreous fluid and human RPE cells. 23 Apo A-I has a protective effect on the corneal epithelium and may improve the epithelial conditions of the ocular surface. 24 Clusterin is also present in human tears.…”