Retinal apoptosis and the effect of tyrosine kinase inhibition in experimental diabetes


  • S. V. Ziablitsev Bogomolets National Medical University
  • V. V. Vodianyk Bogomolets National Medical University



diabetic retinopathy, immunohistochemistry, immunoblotting, streptozotocin, imatinib, caspase-3, Bax, Bcl-xl


Background: It is important to develop orbital hydrogel implants capable of depositing drugs (particularly, antimicrobial and anticancer drugs).

Purpose: To assess antimicrobial effects of hybrid hydrogel implants containing gold nanoparticles and albucide and developed for reconstructive surgery in the orbit and periorbital area.

Material and Methods: A 30% aqueous solution of albucide was used in the study. Antimicrobial activity of synthesized hydrogels was determined using Escherichia coli ATCC 25922, Enterococcus faecalis ATCC 29213, Staphylococcus aureus ATCC 25923 and Pseudomonasa eruginosa ATCC 27853 strains.

Results: All the synthesized samples of orbital hydrogel implants were sterile.

The synthesized hydrogels and hydrogel nanocomposites with incorporated Au nanoparticles demonstrated bacteriostatic effects against E. Coli ATCC 25922, E. Faecalis ATCC 29213, and S. Aureus ATCC 25923 strains, and bactericidal effects against P. Aeruginosa ATCC 27853 strain. This study also demonstrated marked bactericidal effects of hybrid hydrogel implants incorporating both Au nanoparticles and albucide.

Conclusion: Orbital hydrogel implants were found to be sterile after being sealed into polypropylene bags and steam sterilized at 121 °C for 20 minutes. Our findings of bacteriostatic and bactericidal effects of the synthesized hydrogels and hydrogel nanocomposites containing Au nanoparticles and albucide against bacterial strains of interest will allow for the absence of, or low probability of bacterial contamination in applications of these hydrogels in implants.


Wong TY, Sabanayagam C. Strategies to Tackle the Global Burden of Diabetic Retinopathy: From Epidemiology to Artificial Intelligence. Ophthalmologica. 2020;243(1):9-20.

Sun H, Saeedi P, Karuranga S, Pinkepank M, Ogurtsova K, Duncan BB, Stein C, Basit A, Chan JCN, Mbanya JC, Pavkov ME, Ramachandaran A, Wild SH, James S, Herman WH, Zhang P, Bommer C, Kuo S, Boyko EJ, Magliano DJ. IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract. 2022 Jan;183:109119.

Wang W, Lo ACY. Diabetic Retinopathy: Pathophysiology and Treatments. Int J Mol Sci. 2018 Jun 20;19(6):1816.

Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes. 2005 Jun;54(6):1615-25.

Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007 Jun;35(4):495-516.

Eskandari E, Eaves CJ. Paradoxical roles of caspase-3 in regulating cell survival, proliferation, and tumorigenesis. J Cell Biol. 2022 Jun 6;221(6):e202201159.

Van Opdenbosch N, Lamkanfi M. Caspases in Cell Death, Inflammation, and Disease. Immunity. 2019 Jun 18;50(6):1352-1364.

Abu-El-Asrar AM, Dralands L, Missotten L, Al-Jadaan IA, Geboes K. Expression of apoptosis markers in the retinas of human subjects with diabetes. Invest Ophthalmol Vis Sci. 2004 Aug;45(8):2760-6.

Wu W, Xie Z, Zhang Q, Ma Y, Bi X, Yang X, Li B, Chen J. Hyperoside Ameliorates Diabetic Retinopathy via Anti-Oxidation, Inhibiting Cell Damage and Apoptosis Induced by High Glucose. Front Pharmacol. 2020 May 29;11:797.

Hernández C, García-Ramírez M, Corraliza L, Fernández-Carneado J, Farrera-Sinfreu J, Ponsati B, González-Rodríguez A, Valverde AM, Simó R. Topical administration of somatostatin prevents retinal neurodegeneration in experimental diabetes. Diabetes. 2013 Jul;62(7):2569-78.

Gavi S, Shumay Е, Wang Н, Malbon С. G-protein-coupled receptors and tyrosine kinases: crossroads in cell signaling and regulation. Trends Endocrinol Metab. 2006;17(2): 46-52.

Maruyama IN. Mechanisms of activation of receptor tyrosine kinases: monomers or dimers. Cells. 2014 Apr 22;3(2):304-30.

Siddle K. Molecular basis of signaling specificity of insulin and IGF receptors: neglected corners and recent advances. Front Endocrinol (Lausanne). 2012 Feb 28;3:34.

Liu Y, Chen J, Liang H, Cai Y, Li X, Yan L, Zhou L, Shan L, Wang H. Human umbilical cord-derived mesenchymal stem cells not only ameliorate blood glucose but also protect vascular endothelium from diabetic damage through a paracrine mechanism mediated by MAPK/ERK signaling. Stem Cell Res Ther. 2022 Jun 17;13(1):258.

Guo Y, Guo C, Ha W, Ding Z. Carnosine improves diabetic retinopathy via the MAPK/ERK pathway. Exp Ther Med. 2019 Apr;17(4):2641-2647. Epub 2019 Jan 30.

Liu F, Ma Y, Xu Y. Taxifolin Shows Anticataractogenesis and Attenuates Diabetic Retinopathy in STZ-Diabetic Rats via Suppression of Aldose Reductase, Oxidative Stress, and MAPK Signaling Pathway. Endocr Metab Immune Disord Drug Targets. 2020;20(4):599-608.

Hymowitz SG, Malek S. Targeting the MAPK Pathway in RAS Mutant Cancers. Cold Spring Harb Perspect Med. 2018 Nov 1;8(11):a031492.

Waller CF. Imatinib Mesylate. Recent Results Cancer Res. 2018;212:1-27.

Boneva SK, Wolf J, Hajdú RI, Prinz G, Salié H, Schlecht A, et al. In-Depth Molecular Characterization of Neovascular Membranes Suggests a Role for Hyalocyte-to-Myofibroblast Transdifferentiation in Proliferative Diabetic Retinopathy. Front Immunol. 2021 Nov 2;12:757607.

Dabbs D. Diagnostic Immunohistochemistry, 4th Edition Theranostic and genomic applications. 2014. 960 p.

Subburaj Y, Cosentino K, Axmann M, Pedrueza-Villalmanzo E, Hermann E, Bleicken S, Spatz J, García-Sáez AJ. Bax monomers form dimer units in the membrane that further self-assemble into multiple oligomeric species. Nat Commun. 2015 Aug 14;6:8042.

Wang T, Zhang Z, Song C, Sun L, Sui X, Qu Q, Liu J. Astragaloside IV protects retinal pigment epithelial cells from apoptosis by upregulating miR 128 expression in diabetic rats. Int J Mol Med. 2020 Jul;46(1):340-350.

Hombrebueno JR, Ali IH, Xu H, Chen M. Sustained intraocular VEGF neutralization results in retinal neurodegeneration in the Ins2(Akita) diabetic mouse. Sci Rep. 2015 Dec 16;5:18316.

Damian I, Nicoară SD. Correlations between Retinal Arterial Morphometric Parameters and Neurodegeneration in Patients with Type 2 Diabetes Mellitus with No or Mild Diabetic Retinopathy. Medicina (Kaunas). 2021 Mar 5;57(3):244.

Simó R, Stitt AW, Gardner TW. Neurodegeneration in diabetic retinopathy: does it really matter? Diabetologia. 2018 Sep;61(9):1902-1912.

Himasa FI, Singhal M, Ojha A, Kumar B. Prospective for Diagnosis and Treatment of Diabetic Retinopathy. Curr Pharm Des. 2022;28(7):560-569.

Stem MS, Gardner TW. Neurodegeneration in the pathogenesis of diabetic retinopathy: molecular mechanisms and therapeutic implications. Curr Med Chem. 2013;20(26):3241-50.

Shanab AY, Nakazawa T, Ryu M, Tanaka Y, Himori N, Taguchi K, Yasuda M, Watanabe R, Takano J, Saido T, Minegishi N, Miyata T, Abe T, Yamamoto M. Metabolic stress response implicated in diabetic retinopathy: the role of calpain, and the therapeutic impact of calpain inhibitor. Neurobiol Dis. 2012 Dec;48(3):556-67.

Sasaki M, Ozawa Y, Kurihara T, Kubota S, Yuki K, Noda K, Kobayashi S, Ishida S, Tsubota K. Neurodegenerative influence of oxidative stress in the retina of a murine model of diabetes. Diabetologia. 2010 May;53(5):971-9.

Wu C, Xu K, Liu W, Liu A, Liang H, Li Q, Feng Z, Yang Y, Ding J, Zhang T, Liu Y, Liu X, Zuo Z. Protective Effect of Raf-1 Kinase Inhibitory Protein on Diabetic Retinal Neurodegeneration through P38-MAPK Pathway. Curr Eye Res. 2022 Jan;47(1):135-142.



How to Cite

Ziablitsev SV, Vodianyk VV. Retinal apoptosis and the effect of tyrosine kinase inhibition in experimental diabetes. J.ophthalmol. (Ukraine) [Internet]. 2023 Nov. 1 [cited 2024 Jun. 25];(5):34-40. Available from:



Experimental Studies