ISSN 2415-3060 (print), ISSN 2522-4972 (online)
  • 15 of 44
JMBS 2019, 4(2): 100–106
Experimental Medicine and Morphology

Dicarbonyl Stress in Eye Tissue of Rabbits with Ocular Hypertension in Experimental Diabetes

Yurevich V. R. 1, Mikheytseva I. N. 2

A significant damaging molecular mechanism, which is inherent for various associated with age, diabetes, inflammation, is dicarbonyl stress. The abnormal accumulation of dicarbonyl metabolites leads to an enhanced disruption of the structure of biomolecules and causes various dysfunctions, in particular, in diabetes mellitus. The involvement of this pathochemical mechanism in the pathogenesis of an age-related neurodegenerative disease, such as glaucoma, is also of considerable interest. High intraocular pressure (ocular hypertension) is one of the main signs of glaucoma. The purpose of research was to study the level of dicarbonyl metabolites methylglyoxal, glyoxal and the activity of the enzyme glyoxalase-1 in eye tissues (anterior chamber angle, retina and optic nerve) of rabbits with ophthalmic hypertension and experimental diabetes. Material and methods. Experimental studies were conducted on 33 adult rabbits, which were simulated streptozotocin diabetes; ophthalmic hypertension; diabetes and ophthalmic hypertension combined. In the tissues of the anterior chamber angle, the retina and the optic nerve the levels of methylglyoxal, glyoxal and enzyme glyoxalase-1 activity were determined. Diabetes was caused by injection of streptozotocin (65 mg per 1 kg of body weight, intravenously). Ophthalmic hypertension was caused by injection into the anterior chamber of the eye with 0.25 ml of 2% methylcellulose solution. Results and discussion. The obtained results showed a significant accumulation in the tissues of anterior and posterior part of the eye in rabbits with ophthalmic hypertension and diabetes methylglyoxal, glyoxal and a decrease in the activity of the enzyme enzyme glyoxalase-1. The parameters of dicarbonyl stress studied in the tissues of the eye of rabbits were changed more pronounced with the combined modeling of ophthalmic hypertension and streptozotocin diabetes than with the separate modeling of these diseases. In this case, the level of methylglyoxal in the tissues of the anterior chamber angle was increased by 64% compared with the control group, and glyoxal increased by 120%. In the retina and optic nerve methylglyoxal increased by 118%, glyoxal increased by 147%. The minimal activity of glyoxalase -1 was noted in the same group, it was 30% of the data of control animals in the anterior chamber angle tissue. Еnzyme glyoxalase-1 activity of eye neuronal tissues (retina and optic nerve) was about the same low levels and was equal to 32.5% of control values. All changes were statistically significant (p˂0.01). The relationship between the high intracellular content of toxic carbonyl compounds, the rate of formation of the final glycation products and the potential of the glyoxylase system plays a crucial role in the formation of complications of diabetes mellitus and age-related pathologies. We obtained experimental data on the increase in carbonyl stress with proven accumulation of toxic metabolites and a decrease in detoxification the enzyme system in the drainage and neuronal system tissues of the eye with ophthalmic hypertension in diabetes. These results have significant value to clarify the pathogenesis of diseases and the development of targeted treatment. Conclusions. Dicarbonyl stress is a possible pathogenetic mechanism of pathological changes in the eye tissues in glaucoma, which has appeared on the background of diabetes mellitus. Therefore, it is necessary to develop a directed therapeutic influence on this link of pathogenesis in the treatment of this combined pathology.

Keywords: dicarbonyl stress, anterior chamber angle, retina and optic nerve, ocular hypertension, diabetes mellitus

Full text: PDF (Rus) 294K

  1. Astakhov YuS, Krylova IS, Shadrichev FE. Yavlyaetsya li sakharnyy diabet faktorom riska pervichnoy otkrytougolnoy glaukomy? Klinicheskaya oftalmologiya. 2006; 7(3): 91–4. [Russian]
  2. Vorobeva IV, Merkushenkova DA, Kalinina NI, Ivanova DP, Estrin LG. Vzaimosvyaz mezhdu pervichnoy otkrytougolnoy glaukomoy i sakharnym diabetom. Novosti glaukomy. 2012; 24(4): 3–4.
  3. Ahmed N, Thornalley PJ, Dawczynski J, Franke S, Strobel J, Stein G, et al. Methylglyoxal-derived hydroimidazolone advanced glycation endproducts of human lens proteins. Investig Ophthalmol. Vis Sci. 2003; 44(12): 5287–92.
  4. Barati MT, Merchant ML, Kain AB, Jevans AW, McLeish KR, Klein JB. Proteomic analysis defines altered cellular redox pathways and advanced glycation end-product metabolism in glomeruli of db/db diabetic mice. Amer J Physiol Renal Physiology. 2007; 293(4): F1157–65.
  5. Becker B. Diabetes mellitus and primary open-angle glaucoma. Am J Ophthalmol. 1971; 71(1 Pt 1): 1–16.
  6. Berner AK, Brouwers O, Pringle R, Klaassen I, Colhoun L, McVicar C, et al. Protection against methylglyoxal-derived AGEsby regulation of glyoxalase 1 prevents retinal neuroglial and vasodegenerative pathology. Diabetologia. 2012; 55(3): 845–54.
  7. Bierhaus A, Fleming T, Stoyanov S, Leffler A, Babes A, Neacsu C, et al. Methylglyoxal modification of Nav1.8 facilitates nociceptive neuron firing and causes hyperalgesia in diabetic neuropathy. Nat Med. 2012; 18(6): 926–33.
  8. Bonovas S, Peponis V, Filioussi K. Diabetes mellitus as a risk factor for primary open-angle glaucoma: a meta-analysis. Diabetic Medicine. 2004; 21(6): 609–14.
  9. Gülgün Tezel, Luo C, Yang Х. Accelerated Aging in Glaucoma: Immunohistochemical Assessment of Advanced Glycation End Products in the Human Retina and Optic Nerve Head. Invest Ophthalmol Vis Sci. 2007; 48(3): 1201–11.
  10. Hegab Z, Gibbons S, Neyses L, Mamas MA. Role of advanced glycation end products in cardiovascular disease. World J Cardiol. 2012; 4(4): 90–102.
  11. Karachalias N, Babaei-Jadidi R, Rabbani N, Thornalley PJ. Increased protein damage in renal glomeruli, retina, nerve, plasma and urine and its prevention by thiamine and benfotiamine therapy in a rat model of diabetes. Diabetologia. 2010; 53(7): 1506–16.
  12. Mir MS, Darzi MM, Baba OK, Khan HM, Kamil SA, Sofi AH, et al. Streptozotocin Induced Acute Clinical Effects in Rabbits. Iranian J Pathology. 2015; 10(3): 206–13.
  13. McLellan AC, Thornalley PJ, Benn J, Sonksen PH. The glyoxalase system in clinical diabetes mellitus and correlation with diabetic complications. Clin Sci. 1994; 87(1): 21–9.
  14. Miller AG, Tan G, Binger KJ, Pickering RJ, Thomas MC, Nagaraj RH, et al. Candesartan attenuates diabetic retinal vascular pathology by restoring glyoxalase 1 function. Diabetes. 2010; 59(12): 3208–15.
  15. Milne R, Brownstein S. Advanced glycation end products and diabetic retinopathy. Amino Acids. 2011; 44: 1397–407.
  16. Rabbani N, Thornalley PJ. Dicarbonyls (Glyoxal, Methylglyoxal, and 3-Deoxyglucosone). In: Niwa T, Ed by Uremic Toxins. Hoboken. NJ: John Wiley & Sons, Inc; 2012. p. 177–92.
  17. Lee SH, Kim SH, Kim JW. Effect of Methylglyoxal on the Oxidative Stress in Trabecular Meshwork Cells. J Korean Ophthalmol Soc. 2009; 10: 1569-75.
  18. Spoerl E, Boehm AG, Pillunat LE. The influence of various substances on the biomechanical behavior of lamina ctibrosa and peripapillary sclera. IOVS. 2005; 46(4): 1286-90.
  19. Zhu MD, Cai FY. Development of experimental chronic intraocular hypertension in the rabbit. Australian and New Zeland J Ophthalmol. 1992; 20: 225-34.
  20. Zubaty V, Spoerl E, Boehm A, Geiger K, Pillunat L. Increased Advanced Glycation End-Products (AGEs) in Trabecular Meshwork of Patients With Primary and Secondary Glaucoma. Invest Ophthalmol Vis Sci. 2008; 49(13): 1607.