The relationship between levels of apolipoprotein A1 and B in aqueous and serum with stage of diabetic retinopathy

Abstract

Aim: To determine the association between serum and aqueous apolipoprotein (Apo) A1 and Apo B levels and Apo B/A1 ratio in diabetic retinopathy. Material and Method: This cross-sectional prospective study included 63 diabetic patients with or without retinopathy and 38 control subjects who underwent cataract surgery. The study groups were as follows; healthy subjects (Group 1), diabetic patients without retinopathy (Group 2), with non-proliferative diabetic retinopathy (Group 3), and with proliferative diabetic retinopathy (Group 4). Serum and aqueous Apo A1 and Apo B levels were determined by using an enzyme-linked immunosorbent assay. Results: The amount of Apo B was determined in aqueous samples of all (100%) patients in Group 4 and 77.7% of patients in Group 3.The mean serum Apo B/A1 ratio was significantly higher in Group 2, Group 3 and Group 4 compared with Group 1 (p=0.002, p=0.037 and p<0.001, respectively). The aqueous Apo B level, aqueous and serum Apo B/A1 levels were significantly correlated with the severity of retinopathy in diabetic patients (all p<0.001). Conclusion: Higher serum and aqueous Apo B/A1 ratio were significantly associated with the stage of diabetic retinopathy.

Keywords

• aqueous humor
• diabetic retinopathy
• apolipoprotein A1
• apolipoprotein B

References

1. Cheung N, Mitchell P, Wong TY. Diabetic retinopathy. Lancet 2010 Jul 10; 376: 124-36.
2. Vujosevic S, Aldington SJ, Silva P, et al. Screening for diabetic retinopathy: new perspectives and challenges. Lancet Diabetes Endocrinol 2020; 8: 337-47.
3. Ghamdi AHA. Clinical predictors of diabetic retinopathy progression; a systematic review. Curr Diabetes Rev 2020; 16: 242-7.
4. Lyons TJ, Jenkins AJ, Zheng D, et al. Diabetic retinopathy and serum lipoprotein subclasses in the DCCT/EDIC cohort. Invest Ophthalmol Vis Sci 2004; 45: 910-8.
5. Klein R, Sharrett AR, Klein BE, et al. The association of atherosclerosis, vascular risk factors, and retinopathy in adults with diabetes: the Atherosclerosis Risk in Communities Study. Ophthalmology 2002; 109: 1225–34.
6. Zhou Y, Wang C, Shi K, YinX. Relationship between dyslipidemia and diabetic retinopathy: A systematic review and meta-analysis. Medicine (Baltimore) 2018; 97: e12283.
7. Zhang Q, Hu J, Hu Y, et al. Relationship between serum apolipoproteins levels and retinopathy risk in subjects with type 2 diabetes mellitus. Acta Diabetol 2018; 55: 681-9.
8. Simo R, Garcia-Ramirez M, Higuera M, Hernandez C. Apolipoprotein A1 is overexpressed in the retina of diabetic patients. Am J Ophthalmol 2009; 147: 319-25 e1.

9. Simo R, Higuera M, Garcia-Ramirez M, Canals F, Garcia-Arumi J, Hernandez C. Elevation of apolipoprotein A-I and apolipoprotein H levels in the vitreous fluid and overexpression in the retina of diabetic patients. Arch Ophthalmol 2008; 126: 1076-81.
10. Davidson MH. Apolipoprotein measurements: is more widespread use clinically indicated? Clin Cardiol 2009; 32: 482-6.
11. Shah PK, Kaul S, Nilsson J, Cercek B. Exploiting the vascular protective effects of high-density lipoprotein and its apolipoproteins: an idea whose time for testing is coming, part II. Circulation 2001; 104: 2498-502.
12. Marcovina S, Packard CJ. Measurement and meaning of apolipoprotein AI and apolipoprotein B plasma levels. J Intern Med 2006; 259: 437-46.
13. Wu M, Chen Y, Wilson K, et al. Intraretinal leakage and oxidation of LDL in diabetic retinopathy. Invest OphthalmolVis Sci 2008; 49: 2679-85.
14. Hu A, Luo Y, Li T, et al. Low serum apolipoprotein A1/B ratio is associated with proliferative diabetic retinopathy in type 2 diabetes. Graefes Arch Clin Exp Ophthalmol 2012; 250: 957-62.
15. Sasongko MB, Wong TY, Nguyen TT, et al. Serum apolipoprotein AI and B are stronger biomarkers of diabetic retinopathy than traditional lipids. Diabetes Care 2011; 34: 474-9.
16. Sasongko MB, Wong TY, Nguyen TT, et al. Serum apolipoproteins are associated with systemic and retinal microvascular function in people with diabetes. Diabetes 2012; 61: 1785-92.
17. Ankit BS, Mathur G, Agrawal RP, Mathur KC. Stronger relationship of serum apolipoprotein A-1 and B with diabetic retinopathy than traditional lipids. Indian J Endocrinol Metab 2017; 21: 102-5.
18. Chung JO, Park SY, Cho DH, Chung DJ, Chung MY. Associations between serum apolipoproteins, urinary albumin excretion rate, estimated glomerular filtration rate, and diabetic retinopathy in individuals with type 2 diabetes. Medicine (Baltimore) 2019; 98: e15703.
19. Early Treatment Diabetic Retinopathy Study Research Group. Grading diabetic retinopathy from stereoscopic color fundus photographs—an extension of the modified Airlie House classification: ETDRS report number 10: Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology 1991; 98: 786-806.
20. Funatsu H, Yamashita H, Noma H, et al. Aqueous humor levels of cytokines are related to vitreous levels and progression of diabetic retinopathy in diabetic patients. Graef Arch Clin Exp Ophthalmol 2005; 243: 3-8.
21. Barsotti MF, Bartels SP, Freddo TF, Kamm RD. The source of protein in the aqueous humor of the normal monkey eye. Invest Ophthalmol Vis Sci 1992; 33: 581-95.
22. Maurice DM. Flow of water between aqueous and vitreous compartments in the rabbit eye. Am J Physiol 1987; 252: F104–8.
23. Fatt I. Flow and diffusion in the vitreous body of the eye. Bull Math Biol 1975; 37: 85-90.
24. Kawai S, Nakajima T, Hokari S, Komoda T, Kawai K. Apolipoprotein A-I concentration in tears in diabetic retinopathy. Annals Clin Bioch 2002; 39: 56-61.
25. Garcia-Ramirez M, Canals F, Hernandez C, et al. Proteomic analysis of human vitreous fluid by fluorescence-based difference gel electrophoresis (DIGE): a new strategy for identifying potential candidates in the pathogenesis of proliferative diabetic retinopathy. Diabetologia 2007; 50: 1294-303.
26. Crosby-Nwaobi R, Chatziralli I, Sergentanis T, Dew T, Forbes A, Sivaprasad S. Cross Talk between Lipid Metabolism and Inflammatory Markers in Patients with Diabetic Retinopathy. J Diabetes Res 2015; 2015: 191382.
27. Miljanovic B, Glynn RJ, Nathan DM, Manson JE, Schaumberg DA. A prospective study of serum lipids and risk of diabetic macular edema in type 1 diabetes. Diabetes 2004; 53: 2883-92.
28. Keech AC, Mitchell P, Summanen PA, et al. Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial. Lancet 2007; 370: 1687-97.
29. Tserentsoodol N, Sztein J, Campos M, et al. Uptake of cholesterol by the retina occurs primarily via a low density lipoprotein receptor-mediated process. Molecular Vision 2006; 12: 1306-18.
30. Tserentsoodol N, Gordiyenko NV, Pascual I, Lee JW, Fliesler SJ, Rodriguez IR. Intraretinal lipid transport is dependent on high density lipoprotein-like particles and class B scavenger receptors. Molecular vision 2006; 12: 1319-33.
31. Chiang SY, Tsai ML, Wang CY, et al. Proteomic analysis and identification of aqueous humor proteins with a pathophysiological role in diabetic retinopathy. J Proteomics 2012; 75: 2950-9.