J.ophthalmol.(Ukraine).2019;5:56-63.

http://doi.org/10.31288/oftalmolzh201955663

Received: 18 April 2019; Published on-line: 30 October 2019


On the role of lipid metabolism and lipid peroxidation in the development of retinal disorders in type 2 diabetic rats with myopia    

Abdulhadi Mohammad,  Cand. Sc. (Med.); I.N. Mikheitseva, Dr. Sc. (Biol.); S.G. Kolomiichuk, a Research Fellow

SI " The Filatov Institute of Eye Diseases and Tissue Therapy of the NAMS of Ukraine”; Odesa (Ukraine) 

E-mail: filatovbiochem@ukr.net

TO CITE THIS ARTICLE: Abdulhadi Mohammad, Mikheitseva IN, Kolomiichuk SG. On the role of lipid metabolism and lipid peroxidation in the development of retinal disorders in type 2 diabetic rats with myopia. J.ophthalmol.(Ukraine).2019;5:56-63-48.    http://doi.org/10.31288/oftalmolzh201955663

 

Background. There are current data on the role of dyslipidemia and enhanced processes of lipid peroxidation (LPO) in the pathogenesis of diabetic retinopathy (DR). However, pathogenic mechanisms which can explain the link between main parameters of lipid metabolism and development of DR, especially in high myopia, are still understudied. 

Purpose. To study the parameters of lipid metabolism and lipid peroxidation in blood and retina of streptozotocin-induced diabetic rats with deprivation myopia with a purpose to reveal the pathogenetic features of the development of type 2 diabetes mellitus in the presence of myopia.

Material and Methods. The study was performed on Wistar rats. The rabbits were divided into four groups: group 1, 15 rabbits with axial myopia; group 2, 15 rats with diabetes; group 3, 15 rats with myopia and diabetes; 10 intact rats serving as controls. Eyelids of two-week animals (30 rats) were sutured to induce axial myopia, according to Beuerman R.W. et al. The animals were kept under poor light conditions for 14 days. After a fortnight, the sutures were removed. In two weeks, 15 rats with myopia and 15 intact rats were induced type 2 diabetes mellitus (T2DM). T2DM was induced using 5 daily intraperitoneal injections of streptozotocin (15.0 mg per 1 kg). The control rats were kept under natural light condition. The criterion of diabetes onset was an increase in the blood glucose level up to 4.5mmol/L. After two months, the animals were sacrificed under general anesthesia and the eyeballs were enucleated. To assess myopia severity, axial length was measured post mortem using a digital sliding caliper (Topex) with 0.02 mm accuracy. Levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) [16, 17], diene conjugates (DC), and malondialdehyde (MDA) were evaluated in the blood plasma and DC and MDA levels were measured in the retina. The Atherogenic Index (AI) was calculated. Data obtained were processed statistically with the parametric Student-t test using a software program (Statistica).  Results.  Expressed disorders were revealed in lipid metabolism, including increased levels of TC, LDL-C, TG, decreased HDL-C, and those in ratios of metabolic parameters in the blood of STZ diabetic rats with and without myopia. No significant changes in the levels of TC, TG, LDL-C, and HDL-C were noted in the rats with deprivation myopia, which gives evidence that there are no disorders in lipid metabolism in the presence of myopia. Our study revealed no significant difference in lipid profile outcomes between the diabetic-only animals and diabetic animals with myopia. 

Studying LPO parameters in deprivation myopia showed a statistically insignificant increase in the levels of MDA and DC both in the blood plasma and retina of the myopic rats as compared with controls. STZ-induced diabetes resulted in significant changes in the level of LPO products in the rats’ blood plasma and retina. The MDA level was 3.8 times increased in diabetes (р<0.001) and 4.6 times increased in diabetes with myopia (р<0.001) as compared with control. Similar changes were noted in the DC level, which was increased, as compared with control, by 118.8% (р<0.001) and 169.4% (р<0.001) in diabetes only and diabetes with myopia, respectively. Statistically insignificant changes in the levels of LPO were noted in the diabetic rats as compared with the diabetic rats with myopia. 

Conclusions. Disorders in lipid metabolism parameters in the peripheral blood were revealed both in SZT-induced diabetes and in SZT-induced diabetes in combination with axial myopia. There was no significant difference in lipid metabolism markers between groups with diabetes only and diabetes with axial myopia. Thus, the presence of axial myopia does not worsen lipid metabolism in the SZT-induced diabetic rats. The experiment confirmed the fact that lipid peroxidation is activated in the blood and retina of the SZT-induced diabetic rats; it is also activated in diabetes developed against axial myopia. No significant difference was revealed in the LPO parameters between diabetic rats with and without myopia. 

Keywords: deprivation myopia, type 2 diabetes mellitus, retina, parameters of lipid metabolism, lipid peroxidation, rats, experiment

References

1.[Diabetes Mellitus: acute and chronic complications]. Edited by Dedov I.I., Shestakova M.V. Moscow: Med. Inform. Agenstvo;2012. 480p. In Russian.   

2.Chang YC, Wu WC. Dyslipidemia and Diabetic Retinopathy. The Review of Diabetic Studies. 2013;10(2–3):121–32.

Crossref   PubMed

3.Mikaeliyan NP, Gurina AE, Nguen NZ et al. [The relationship between process of peroxidation of lipids, activity of antioxidant system and fatty-acid composition of blood in patients with diabetes mellitus type I and under its complications]. Ros. Med. Zhurn. 2014;4:33-8. In Russian.  

4.Mikaelyan NP, Potemkin VV. [The metabolic disorders in membrane of erythrocytes and insulin-binding activity of blood cells in patients under obesity and diabetes mellitus type II]. Ros. Med. Zhurn. 2017;23(4):201-4. In Russian.   

Crossref   

5.Aldebasi YH, Mohieldein АН, Almansour YS, Almutairi BL. Dyslipidemia and lipid peroxidation of Saudi type 2 diabetics with proliferative retinopathy. Saudi Med. J. 2013;34(6): 616–22.

6.Zhou Yue, Changyun Wang, Ke Shi et al. Relationship between dyslipidemia and diabetic retinopathy A systematic review and meta-analysis. Medicine (Baltimore). 2018; Sep; 97(36): e12283. Published online 2018 Sep 7. 

Crossref    PubMed  

7.Klein BE, Moss SE, Klein R, Surawicz TS. The Wisconsin Epidemiologic Study of Diabetic Retinopathy. XIII. Relationship of serum cholesterol to retinopathy and hard exudates. Ophthalmology. 1991;98(8):1261–5.

Crossref   

8.Tayyab H, Haider МА, Bukhari Shaheed, Haider SА. Axial myopia and its influence on diabetic retinopathy. J. Coll. Physicians Surg. Pak. 2014. Oct; 24(10): 728-31. doi: 10.2014/JCPSP.728731.

9.Wang X, Tang L, Gao L, Yang Y, Cao D, Li Y. Myopia and diabetic retinopathy: A systematic review and meta-analysis. Diabetes Res Clin Pract. 2016 Jan;111:1-9. doi: 10.1016/j.diabres.2015.10.020. Epub 2015 Oct 23.

Crossref   PubMed  

10.Wat N, Wong RL, Wong IY. Associations between diabetic retinopathy and systemic risk factors. Hong Kong Med. J. 2016. 22(6):589-99. 

Crossref   

11.Bazzazi N, Akbarzadeh S, Yavarikia М et al. High myopia and diabetic retinopathy: A Contralateral Eye Study in Diabetic Patients With High Myopic Anisometropia. Retina. 2017. Jul; 37(7):1270-6. 

Crossref   

12.Beuerman RW, Maw SS, Tan DT et al. Myopia: animal models to clinical trials. Singapore World Scientific; 2010. 390 p.

13.Mikheytseva IN, Abdulhadi Mohammad, Putienko АА et al.  Modelling form deprivation myopia in experiment. J.ophthalmol.(Ukraine).2018;2:50-55.

Crossref   

14.Kovaleva MA, Kryshen KL, Makarova MN, Makarov VG. [Age of formation of streptozotocin-induced diabetes in rats]. Mezhdunarodnyi vestnik veterinarii. 2014;4:90-6. In Russian.  

15.Kolbina MV, Chesnokov VI, Dolgich VT. [The particularities of model ingof type 2 diabetes mellitusin rats]. Vestnik KazNMU.2013;5(1):145-7. In Russian.  

16.Chaialo PP. [Disorders of lipoprotein metabolism]. K.:Zdorovya;1990. 184p. In Russian.  

17.Goriachkovskii AM. [Clinical biochemistry in laboratory diagnostics]. Odessa:Ekologiia; 2005. 616p. In Russian. 

18.Orekhovich VN. [Modern methods in biochemistry]. Moscow: Meditsina; 1977: 392p. In Russian. 

19.Enomoto М, Adachi H, Hirai Y et al. LDL-C/HDL-C Ratio Predicts Carotid Intima-Media Thickness Progression Better Than HDL-C or LDL-C Alone. J. Lipids. 2011. Article ID 549137, 6 pages

Crossref    PubMed   

20.Haymana С, Sonmez A, Aydoqdu A et al. Visceral adiposity index and triglyceride/high-density lipoprotein cholesterol ratio in hypogonadism. Arch Endocrinol Metab. 2017; 61(3):282 – 7.

Crossref   PubMed

21.Cowie CC, Harris MI. Physical and metabolic characteristics of persons with diabetes. Diabetes in America. 2nd ed. Washington (DC): National Institutes of Health, 1995:117–64. 

Crossref   

22.Syv?nne M, Taskinen MR. Lipids and lipoproteins as coronary risk factors in non-insulin-dependent Diabetes mellitus. Lancet. 1997; 350:20–3. 

Crossref   

23.Solano MP, Goldberg RB. Management of dyslipidemia in diabetes. Cardiol. Rev. 2006;14:125–35.

Crossref   PubMed   

24.Protasov KV. [Atherogenic dyslipidemia in diabetes mellitus. Part 1: pathogenesis, clinical and prognostic significance, lipid level monitoring indices]. Sibirskii Med. zhurn. 2012;5:5-9. In Russian. 

25.Eun Bi Kim, Ha Kyoung Kim, Joon Young Hyon et al.  Oxidative Stress Levels in Aqueous Humor from High Myopic Patients. Korean J. Ophthalmol. 2016; 30(3):172–9.

Crossref    PubMed

26.Boichuk I. M., Surovaya K. I., Kolomijchuk S. G. [Content of the free and connected albuminous sulfide and disulfide groups in tear fluid depending on the degree of myopia in children]. Oftalmol Zh. 2015;1:41-4. In Russian. 

Crossref   

27.Khamnagdayeva NV, Obrubov SA, Semenova LY et al. [Regularities of changes in the levels of malondialdehyde and retinol in blood serum of children with myopia in case of poly-morbidity]. Ros. detskaia oftalmologiia.2017;1:35-9. In Russian. 

28.Micelli-Ferrari T, Vendemiale G, Grattagliano I et al. Role of lipid peroxidation in the pathogenesis of myopic and senile cataract. British Journal of Ophthalmology. 1996;80(9):840–3.

Crossref    PubMed  

29.Sies H. Oxidative stress: a concept in redox biology and medicine. Redox Biol. 2015:4:180–3. 

Crossref    PubMed  

30.Seghrouchi I, Dari J, Bannier Е et al. Oxidative stress parameters in type 1, type 2 and insulin-treated type 2 diabetes mellitus; insulin treatment efficacy. Clin Chim Acta. 2002;321:89–96.

Crossref    

31.Cui Y, Хu Х, Zhu Q et al. Expression modification of uncoupling proteins and MnSOD in retinal endothelial cells and pericytes induced by high glucose: the role of reactive oxygen species in diabetic retinopathy. Experimental Eye Research. 2006;83(4):807–16. 

Crossref    PubMed   

32.Yuri KS, Paula HО, Kleber Eduardo de Campos et al. Neonatally-induced diabetes: lipid profile outcomes and oxidative stress status in adult rats. Rev. Assoc. Med. Bras. 2009; 55(4):384–8. 

Crossref    PubMed  

33.Samoilova YuG, Yurchenko YeV. [Characteristics of lipid metabolism in patients with type 1 diabetes, depending on the availability of diabetic microangiopathy and diet]. Bulleten sibirskoi meditsiny. 2014;5:87-92. In Russian.  

34.Syomshchikov VS, Khamnueva LYu,  Chugunova  EV. [Abnormality of lipid metabolism in patients with diabetes mellitus type 1 and poor glycemic control with and without diabetic microangiopathies]. Acta Biomedica Scientifica. 2016;1(6):113-17. In Russian.  

Crossref   

35.Nagra PK, Ho АС, Dugan JDJr. Lipemia retinalis associated with branch retinal vein occlusion. Am. J. Ophthalmol. 2003;135:539–42.

Crossref   

36.Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature. 2001;414(6865): 813–20.

Crossref   PubMed   

37.Novitsky VV, Kravets YeВ, Kolosova MV et al. [The lipid spectrum of erythrocyte membranes in children with diabetes mellitus]. Problemy endokrinologii. 2006;52(4):3-6. In Russian.  

38.Potemkin VV, Frantseva EYu., Kulaieva IO, Mikaelyan NP. [Functional state of membrane-receptor system of the blood in newly diagnosed type 2 diabetes mellitus].  Problemy endokrinologii. 2012;4(2):40-1. In Russian.  

39.Ceriello А, Esposito К, Ihnat М et al. Long-term glycemic control influences the long-lasting effect of hyperglycemia on endothelial function in type 1 diabetes. J. Clin. Endocrinol. Metab. 2009;94(8):2751–6. 

Crossref   PubMed   

40.Pannicke Т, Iandiev I, Wurm А et al. Diabetes alters osmotic swelling characteristics and membrane conductance of glial cells in rat retina. Diabetes. 2006;55(3):633–9. 

Crossref   PubMed

 

The authors certify that they have no conflicts of interest in the subject matter or materials discussed in this manuscript.