• Users Online: 530
  • Home
  • Print this page
  • Email this page
Home Current issue Ahead of print Search About us Editorial board Archives Submit article Instructions Subscribe Contacts Login 

 Table of Contents  
Year : 2013  |  Volume : 106  |  Issue : 4  |  Page : 245-248

Evaluation of the role of apelin in diabetic retinopathy

1 Department of Ophthalmology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
2 Department of Physiology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
3 Department of Internal Medicine, Faculty of Medicine, Zagazig University, Zagazig, Egypt

Date of Submission10-Jul-2013
Date of Acceptance10-Nov-2013
Date of Web Publication28-Apr-2014

Correspondence Address:
Waleed Mahdy Nada
MD, 167 St. Saleh Elsalhy, El Knayat, El Sharkia
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2090-0686.131587

Rights and Permissions

The study was designed to evaluate the role of apelin in diabetic retinopathy by measuring the concentration of plasma apelin and correlating the results between the control group, diabetic patients without and with retinopathy, and diabetic patients after treatment with panretinal photocoagulation (PRP).
The study included four groups: group A consisted of 20 normal individuals as the control group, group B consisted of 20 diabetic patients without retinopathy, group C consisted of 20 diabetic patients with untreated proliferative diabetic retinopathy (PDR), and group D consisted of the same patients of group C after treatment with PRP. Plasma apelin was measured in all groups and interpretation of the results was carried out.
The study revealed that plasma apelin increased significantly in diabetic patients with PDR (mean 1.6 ng/ml) compared with the control group (mean 0.98 ng/ml) and with diabetic patients without retinopathy (mean 0.97 ng/ml). Plasma apelin decreased nonsignificantly in diabetic patient with PDR after treatment with PRP (mean 1.2 ng/ml).
Apelin plays an important role in retinal angiogenesis in diabetic patients; measurement of plasma apelin may be a good indicator for ischemic retinal condition, especially in the absence of other ischemic manifestations in the body.

Keywords: Apelin, diabetic retinopathy

How to cite this article:
Nada WM, Moety DA, Abo Almeaty MM, Hadhoud KM. Evaluation of the role of apelin in diabetic retinopathy. J Egypt Ophthalmol Soc 2013;106:245-8

How to cite this URL:
Nada WM, Moety DA, Abo Almeaty MM, Hadhoud KM. Evaluation of the role of apelin in diabetic retinopathy. J Egypt Ophthalmol Soc [serial online] 2013 [cited 2020 Jun 5];106:245-8. Available from: http://www.jeos.eg.net/text.asp?2013/106/4/245/131587

  Introduction Top

Diabetic retinopathy and retinal neovascularization are considered one of the main challenges by many ophthalmologists, as it is considered one of the leading causes of blindness in many countries [1],[2]. Since the landmark study by Aiello et al. [3] on the association between elevated intraocular concentrations of vascular endothelial growth factor (VEGF) and proliferative diabetic retinopathy, VEGF has been considered the most important primary mediator of retinal angiogenesis. It remains unclear, however, whether other substances also play a primary role in the process of ischemia-induced retinal neovascularization.

Apelin is an endogenous ligand for the angiotensin-1-like receptor. It was first identified from bovine stomach extracts in 1998 [4]. Before its isolation, the angiotensin-1-like receptor was referred to as an orphaned G-protein-coupled receptor because its endogenous ligand was not identified yet. Apelin mRNA and immunoreactive apelin were detected in various tissues and organs. Apelin was shown to affect many biological functions in mammals, such as adjusting the neuroendocrine, cardiovascular, and immune systems by autocrine, paracrine, endocrine, and exocrine signaling [5],[6]. Apelin has various isoforms; the most widely studied are apelin-13 and apelin-36, with apelin-13 invariably exhibiting greater degrees of biological potency than apelin-36 [7].

Apelin has been reported to regulate angiogenesis both in vitro and in vivo. In vitro, apelin was found to stimulate the proliferation and migration of retinal endothelial cells and vascular tube formation [8]. It is responsible for embryonic angiogenesis in the developing retina through autocrine signaling in the endothelial cells, providing a mechanism for regulating the growth of new blood vessel [9].

Tao et al. [10] reported that the concentration of apelin was significantly higher in vitreous and plasma of patients with proliferative diabetic retinopathy; they attributed the results to the fact that apelin was one of the angiogenic factors that plays a role in proliferative diabetic retinopathy.

The present study was designed to evaluate the role of plasma apelin in patients with proliferative diabetic retinopathy and also to correlate its concentration with response to treatment by panretinal photocoagulation (PRP).

  Methods Top

The study was a prospective randomized controlled study that was conducted in Ophthalmology and Internal Medicine Departments in association with Physiology Department, Faculty of Medicine, Zagazig University.

The study was conducted according to the review of medical ethics in accordance with the Declaration of Helsinki and the principle of good clinical practice. Informed consent was obtained after giving detailed information about the study.

The study included four groups; each group consisted of 20 individuals.

Group A included 20 healthy (nondiabetic) individuals as the control group; they were selected on the basis of the following inclusion criteria:

  1. Normal laboratory findings: fasting and postprandial blood glucose level, glycosylated hemoglobin, blood urea and serum creatinine, liver function tests, and lipid profile.
  2. Normal internal medical examination.

The studied groups of patients included 40 diabetic patients fulfilling the following criteria:

  1. No previous retinal treatment.
  2. No previous intraocular surgery.
  3. No significant cataract obscuring the fundus details.
  4. No other ischemic conditions in the body on the basis of clinical medical examination and laboratory investigations.

Patient groups were subjected to clinical medical examination, laboratory investigations including fasting and postprandial blood glucose, glycosylated hemoglobin, liver function tests, blood urea, serum creatinine, and lipid profile. In addition, they were subjected to ophthalmological examination and fluorescene angiography. According to the previous data, the patients were divided into the following groups:

Group B included 20 diabetic patients without retinopathy.

Group C included 20 diabetic patients with untreated proliferative diabetic retinopathy.

Group D included the same 20 patients of group C 1 month after treatment with PRP, with 900-1400 burns, 200-250 μm spot size, and energy of 250-600 MW (Nidek double frequency Yag Laser GYC-1000).

All groups were subjected to determination of plasma apelin level by collecting samples of 3-5 ml venous blood and centrifuging at 3000 rpm for 10 min at 4°C; the liquid component without the sediment was immediately stored at −80°C. Plasma apelin levels were measured using ELISA kits of human Apelin-13 (AP-13 ELISA Kits) MBS 731563 (MyBioSource Inc.) with the following criteria:

  1. Typical sensitivity: 0.1 ng/ml.
  2. Range: 0-100 ng/ml.

Statistical analysis was carried out using the paired and unpaired t-test and by P-value determination.

  Results Top

The demographic data of the studied groups revealed that the mean age and sex distribution in group A (the control group) were 55.2 years, 65% male individuals, 35% female individuals; in group B (diabetic patients without retinopathy) were 55.4 years, 35% male patients, 65% female patients; and in group C (patients with PDR) were 59.7 years, 30% male patients, and 70% female patients.

The mean duration of diabetes in group B patients was 5.7 ± 3.6 years in comparison with 15.3 ± 4.5 years in group C; the increase in the duration in group C with PDR was statistically highly significant (P = 0.000) [Table 1].
Table 1: Demographic data among the groups

Click here to view

Measurement of plasma apelin in groups A, B, and C revealed that the mean plasma apelin in group A (control) was 0.98 ± 0.42 ng/ml, which was nearly the same (0.97 ± 0.3 ng/ml) as in group B (patients without retinopathy), but it was statistically significantly increased in group C (patients with PDR) to 1.6 ± 0.5 ng/ml (P = 0.01) [Table 2].
Table 2: Plasma aplein among the studied groups

Click here to view

Measurement of plasma apelin in group C (untreated PDR) and group D (after treatment by PRP) revealed that the mean plasma apelin before treatment was 1.6 ± 0.5 ng/ml that decreased to 1.2 ± 0.3 ng/ml after 1 month of treatment, but it was statistically insignificant (P = 0.1) [Table 3].
Table 3: Plasma aplein in patients of groups C and D with PDR before and after treatment

Click here to view

  Discussion Top

The present study was conducted to measure plasma apelin in diabetic patients without retinopathy, with PDR, and also after treatment with PRP to report the pathological role of apelin in angiogenic eye diseases. The study by Kasai [11] who stated that apelin may be a crucial factor for pathological retinal angiogenesis is in agreement with the present study revealing that plasma apelin increased significantly in patients with PDR compared with the patients without retinopathy and with the control group. In addition, the present study is in agreement with the study by Edram et al. [12] who stated that plasma apelin increased in patients with poor control of diabetes and PDR; they also stated that it may be decreased in diabetic patients, especially newly diagnosed. This may explain the result of the present study that there was no difference in plasma apelin between diabetic patients with and without retinopathy.

However, the present study is not in agreement with the study by Tao et al. [10] who stated that the concentration of apelin was higher in vitreous samples of patients with PDR in comparison with patients without retinopathy and control individuals, but there was no significant difference in plasma apelin between the different groups previously mentioned. In addition, we agreed with Tao and colleagues in their explanation that the discrepancies between the studies may be because of the differences in patient's inclusion criteria and the duration of diabetes.

The present study revealed that, after treatment with anti-VEGF and PRP, the concentration of plasma apelin decreased nonsignificantly but did not reach the level observed in control individuals and diabetic patients without retinopathy. This result is in agreement with the reported data of the study by Kasai [11] and Tao et al. [10] who stated that apelin is considered as an angiogenic factor in PDR, but the present study did not report a significant decrease in plasma apelin after treatment. It may be because of many factors such as the duration of measurement, which was 1 month after treatment; it may need longer duration such as 4-6 months. In addition, there may be another ischemic mechanism in the body, playing another role in plasma apelin concentration. Another confirmation test may be required to achieve significant results by measuring the apelin level in vitreous samples of patients subjected to vitrectomy.

  Conclusion Top

Apelin played an important role in the progression of retinal angiogenesis in diabetic patients, and measurement of plasma apelin, which is easy and readily available, may have a role in follow-up of diabetic patients, especially with retinopathy. It may be considered a good indicator for ischemic retinal condition but in the absence of other ischemic conditions in the body.

  Acknowledgements Top

Conflicts of interest

There are no conflicts of interest.

  References Top

1.Negi A, Vernon SA. An overview of the eye in diabetes. J R Soc Med 2003; 96:266-272.  Back to cited text no. 1
2.Tielsch JM, Sommer A, Witt K. Blindness and visual improvement in an American urban population: the Baltimore Eye Survey. Arch Ophthalmol 1999; 108:286-290.  Back to cited text no. 2
3.Aiello LP, Avery RL, Arrigg PG. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorder. N Engl J Med 1994; 331:1480-1487.  Back to cited text no. 3
4.Tatemoto K, Hosoya M, Habata Y. Isolation of a novel endogenous peptide ligand for the human APJ receptor. Biochem Biophys Res Commun 1998; 251 : 471-476.  Back to cited text no. 4
5.De Falco M, De Luca L, Onori N. Apelin expression in normal human tissues. In Vivo 2002; 16:333-336.  Back to cited text no. 5
6.Sorli SC, Van den Berghe L, Marsi B. Therapeutic potential of interfering with apelin signaling. Drug Discov Today 2006; 11:1100-1110.  Back to cited text no. 6
7.Simpkin JC, Yellon MD, Davidson SM. Apelin-13 and Apelin-36 exhibit direct cardiovascvular activity against ischemia-perfusion injury. Basic Res Cardiol 2007; 102:518-528.  Back to cited text no. 7
8.Kasani A, Shintani N, Oda M. Apelin is a novel angiogenic factor in retinal endothelial cells. Biochem Biophys Res Commun 2004; 325:395-400.  Back to cited text no. 8
9.Cox CM, D′Agostino SL, Miller MK. Apelin, the ligand for endothelial G protein - coupled receptor, APJ is apotent angiogenic factor required for normal vascular development of the flog embryo. Dev Biol 2006; 296:177-189.  Back to cited text no. 9
10.Tao Y, Lu Q, Jiang Y-R, Qian J, Wang J, Gao L, Jonas JB. Apelin in plasma and in fibrovascular retinal membrane of patients with proliferative diabetic retinopathy. Invest Ophthalmol Vis Sci 2010; 8:4237-4242.  Back to cited text no. 10
11.Kasai A. Pathological rule of apelin in angiogenic eye disease. Yakugaku Zasshi 2011; 131:1201-1206.  Back to cited text no. 11
12.Edram G, Dogru T, Tasci I. Low plasma apelin levels in newly diagnosed type 2 diabetes mellitus. Exp Clin Endocrinol Diabetes 2008; 116:289-292.  Back to cited text no. 12


  [Table 1], [Table 2], [Table 3]

This article has been cited by
1 Elevated blood apelin levels in type 2 diabetes mellitus: A systematic review and meta-analysis
Ali Noori-Zadeh,Salar Bakhtiyari,Shokoufeh Khanjari,Karimeh Haghani,Shahram Darabi
Diabetes Research and Clinical Practice. 2019; 148: 43
[Pubmed] | [DOI]


Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  In this article
Article Tables

 Article Access Statistics
    PDF Downloaded162    
    Comments [Add]    
    Cited by others 1    

Recommend this journal