Top

International Ophthalmology

Published in:

01-12-2017 | Original Paper

Effects of alpha-lipoic acid on retinal ganglion cells, retinal thicknesses, and VEGF production in an experimental model of diabetes

Authors: Emrah Kan, Ömer Alici, Elif Kılıç Kan, Ahmet Ayar

Published in: International Ophthalmology | Issue 6/2017

Abstract

Purpose

The purpose of the present study was to investigate the effect of alpha-lipoic acid (ALA) on the thicknesses of various retinal layers and on the numbers of retinal ganglion cells and vascular endothelial growth factor levels in experimental diabetic mouse retinas.

Methods

Twenty-one male BALB/C mice were made diabetic by the intraperitoneal administration of streptozotocin (200 mg/kg). One week after the induction of diabetes, the mice were divided randomly into three groups: control group (non-diabetic mice treated with alpha-lipoic acid, n = 7), diabetic group (diabetic mice without treatment, n = 7), and alpha-lipoic acid treatment group (diabetic mice with alpha-lipoic acid treatment, n = 7). At the end of the 8th week, the thicknesses of the inner nuclear layer (INL), outer nuclear layer (ONL), and full-length retina were measured; also retinal ganglion cells and VEGF expressions were counted on the histological sections of the mouse retinas and compared with each other.

Results

The thicknesses of the full-length retina, ONL, and INL were significantly reduced in the diabetic group compared to the control and ALA treatment groups (p = 0.001), whereas the thicknesses of these layers did not show a significant difference between ALA treatment and control groups. The number of ganglion cells in the diabetic group was significantly lower than those in the control and ALA treatment groups (p = 0.001). The VEGF expression was significantly higher in the diabetic group and mostly observed in the ganglion cell and inner nuclear layers compared to the control and ALA treatment groups (p = 0.001). Therefore, the number of ganglion cells and VEGF levels did not show significant differences between the ALA treatment and control groups (p = 0.7).

Conclusions

Our results show that alpha-lipoic acid treatment may have an impact on reducing VEGF levels, protecting ganglion cells, and preserving the thicknesses of the inner and outer layers in diabetic mouse retinas.

Di Leo MA, Ghirlanda G, Gentiloni Silveri N, Giardina B, Franconi F, Santini SA (2003) Potential therapeutic effect of antioxidants in experimental diabetic retina: a comparison between chronic taurine and vitamin E plus selenium supplementations. Free Radic Res 37:323–330CrossRefPubMed

Xu X, Zhu QI, Xia X, Zhang S, Gu Q, Luo D (2004) Blood-retinal barrier breakdown induced by activation of protein kinase C via vascular endothelial growth factor in streptozotocin-induced diabetic rats. Curr Eye Res 28:251–256CrossRefPubMed

Lee P, Wang CC, Adamis AP (1998) Ocular neovascularization: an epidemiologic review. Surv Ophthalmol 43:245–269CrossRefPubMed

Pe’er J, Shweiki D, Itin A, Hemo I, Gnessin H, Keshet E (1995) Hypoxia-induced expression of vascular endothelial growth factor by retinal cells is a common factor in neovascularizing ocular diseases. Lab Invest 72:638–645PubMed

Obrosova IG, Minchenko AG, Marinescu V, Fathallah L, Kennedy A, Stockert CM, Frank RN et al (2001) Antioxidants attenuate early up regulation of retinal vascular endothelial growth factor in streptozotocin-diabetic rats. Diabetologia 44:1102–1110CrossRefPubMed

Pierce EA, Avery RL, Foley ED, Aiell LP, Smith LE (1995) Vascular endothelial growth factor/vascular permeability factor expression in mouse model of retinal neovascularization. Proc Natl Acad Sci USA 92:905–909CrossRefPubMedPubMedCentral

Funatsu H, Yamashita H (2002) Pathophysiology of diabetic retinopathy. Drug News Perspect 15:633–639CrossRefPubMed

Packer L, Kraemer K, Rimbach G (2001) Molecular aspects of lipoic acid in the prevention of diabetes complications. Nutrition 17:888–895CrossRefPubMed

Santos JM, Kowluru RA (2011) Role of mitochondria biogenesis in the metabolic memory associated with the continued progression of diabetic retinopathy and its regulation by lipoic acid. Invest Ophthalmol Vis Sci 52:8791–8798CrossRefPubMedPubMedCentral

10.

Obrosova IG, Fathallah L, Liu E, Nourooz-Zadeh J (2003) Early oxidative stress in the diabetic kidney: effect of DL-(alpha)-lipoic acid. Free Rad Biol Med 34:186–195CrossRefPubMed

11.

Kowluru RA, Chan PS (2007) Oxidative stress and diabetic retinopathy. Exp Diabetes Res 2007:43603PubMedPubMedCentral

12.

Mohammad G, Kowluru RA (2010) Matrix metalloproteinase-2 in the development of diabetic retinopathy and mitochondrial dysfunction. Lab Invest 90:1365–1372CrossRefPubMedPubMedCentral

13.

Asnaghi V, Gerhardinger C, Hoehn T, Adeboje A, Lorenzi M (2003) A role for the polyol pathway in the early neuroretinal apoptosis and glial changes induced by diabetes in the rat. Diabetes 52:506–511CrossRefPubMed

14.

Engerman RL, Kern TS (1987) Progression of incipient diabetic retinopathy during good glycemic control. Diabetes 36:808–812CrossRefPubMed

15.

Kowluru RA, Tang J, Kern TS (2001) Abnormalities of retinal metabolism in diabetes and experimental galactosemia VII. Effect of long-term administration of antioxidants on the development of retinopathy. Diabetes 50:1938–1942CrossRefPubMed

16.

Kawabata T, Packer L (1994) Alpha-lipoate can protect against glycation of serum albumin, but not low density lipoprotein. Biochem Biophys Res Commun 30:99–104CrossRef

17.

Suzuki YJ, Tsuchiya M, Packer L (1992) Lipoate prevents glucose-induced protein modifications. Free Radic Res Commun 17:211–217CrossRefPubMed

18.

Kowluru RA, Odenbach S (2004) Effect of long-term administration of alpha-lipoic acid on retinal capillary cell death and the development of retinopathy in diabetic rats. Diabetes 53:3233–3238CrossRefPubMed

19.

Kawasaki A, Han MH, Wei JY, Hirata K, Otori Y, Barnstable CJ (2002) Protective effect of arachidonic acid on glutamate neurotoxicity in rat retinal ganglion cells. Invest Ophthalmol Vis Sci 43:1835–1842PubMed

20.

Lafuente MP, Villegas-Perez MP, Selles-Navarro I, Mayor- Torroglosa S, Miralles de Imperial J, Vidal-Sanz M (2002) Retinal ganglion cell death after acute retinal ischemia is an ongoing process whose severity and duration depends on the duration of the insult. Neuroscience 109:157–168CrossRefPubMed

21.

Zhen SJ, Howel L, Hatala DA, Huang K, Kern TS (2007) Salicylate-based anti-inflammatory drugs inhibit the early lesion of diabetic retinopathy. Diabetes 56:337–345CrossRef

22.

Martin PM, Roon P, Van Ells TK, Ganapathy V, Smith SB (2004) Death of retinal neurons in streptozotocin-induced diabetic mice. Invest Ophthalmol Vis Sci 45:3330–3336CrossRefPubMed

23.

Barber AJ, Lieth E, Khin SA, Antonetti DA, Buchanan AG, Gardner TW (1998) Neural apoptosis in the retina during experimental and human diabetes. Early onset and effect of insulin. J Clin Invest 102:783–791CrossRefPubMedPubMedCentral

24.

Park SH, Park JW, Park S (2003) Apoptotic death of photoreceptors in the streptozotocin-induced diabetic rat retina. Diabetologia 46:1260–1268CrossRefPubMed

25.

Caldwell RB, Bartoli M, Behzadian MA, El-Remessy AE, Al-Shabrawey M, Platt DH, Caldwell RW (2003) Vascular endothelial growth factor and diabetic retinopathy: pathophysiological mechanisms and treatment perspectives. Diabetes Metab Res Rev 19:442–455CrossRefPubMed

26.

Nakamura N, Hasegawa G, Obayashi H, Yamazaki M, Ogata M, Nakano K, Yoshikawa T et al (2003) Increased concentration of pentosidine, an advanced glycation end product, and interleukin-6 in the vitreous of patients with proliferative diabetic retinopathy. Diabetes Res Clin Pract 61:93–101CrossRefPubMed

27.

Cohen MP, Hud E, Wu VY, Shearman CW (2008) Amelioration of diabetes-associated abnormalities in the vitreous fluid by an inhibitor of albumin glycation. Invest Ophthalmol Vis Sci 49:5089–5093CrossRefPubMed

28.

Frank RN, Amin R, Kennedy A, Hohman T (1997) An aldose reductase inhibitor and aminoguanidine prevent vascular endothelial growth factor expression in rats with long-term galactosemia. Arch Ophthalmol 115:1036–1047CrossRefPubMed

29.

Obrosova IG, Fathallah L, Greene DA (2000) Early changes in lipid peroxidation and antioxidative defense in diabetic rat retina: effect of d-l-alpha-lipoic acid. Eur J Pharmol 9:139–146CrossRef

30.

Lee SG, Lee CG, Yun IH, Hur DY, Yang JW, Kim HW (2012) Effect of lipoic acid on expression of angiogenic factors in diabetic rat retina. Clin Exp Ophthalmol 40:47–57CrossRef

31.

Nebbioso M, Federici M, Rusciano D, Evangelista M, Pescosolido N (2012) Oxidative stress in preretinopathic diabetes subjects and antioxidants. Diabetes Technol Ther 14:257–263CrossRefPubMed

32.

Johnsen-Soriano S, Garcia-Pous M, Arnal E, Sancho-Tello M, Garcia-Delpech S, Miranda M, Bosch-Morell F et al (2008) Early lipoic acid intake protects retina of diabetic mice. Free Radic Res 42:613–617CrossRefPubMed

33.

Harrison EH, McCormick DB (1974) The metabolism of dl-(1,6-14C)lipoic acid in the rat. Arch Biochem Biophys 160:514–522CrossRefPubMed

34.

Ziegler D, Low PA, Litchy WJ, Boulton AJ, Vinik AI, Freeman R, Samigullin R et al (2011) Efficacy and safety of antioxidant treatment with α-lipoic acid over 4 years in diabetic polyneuropathy: the NATHAN 1 trial. Diabetes Care 9:2054–2060CrossRef

Title: Effects of alpha-lipoic acid on retinal ganglion cells, retinal thicknesses, and VEGF production in an experimental model of diabetes
Authors: Emrah Kan
Ömer Alici
Elif Kılıç Kan
Ahmet Ayar
Publication date: 01-12-2017
Publisher: Springer Netherlands
Published in: International Ophthalmology / Issue 6/2017
Print ISSN: 0165-5701
Electronic ISSN: 1573-2630
DOI: https://doi.org/10.1007/s10792-016-0396-z

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Effects of alpha-lipoic acid on retinal ganglion cells, retinal thicknesses, and VEGF production in an experimental model of diabetes

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 6/2017

Characteristics of higher-order aberrations and anterior segment tomography in patients with pathologic myopia

Allogenic cultivated limbal stem cell transplantation versus cadaveric keratolimbal allograft in ocular surface disorder: 1-year outcome

Corneal densitometry and its correlation with age, pachymetry, corneal curvature, and refraction

Influence of aqueous humor convection current on IOL opacification

High-definition dacryoendoscopic features of a canalicular squamous papilloma

Consistent pattern in positional instability of polyfocal full-optics accommodative IOL