Morphometric analysis of retinal structural components in rabbits in experimental diabetes mellitus

Authors

  • O. E. Dorokhova Filatov Institute of Eye Diseases and Tissue Therapy of the National Academy of Medical Sciences of Ukraine image/svg+xml https://orcid.org/0000-0002-7255-012X
  • L. I. Samoilenko Filatov Institute of Eye Diseases and Tissue Therapy of the National Academy of Medical Sciences of Ukraine image/svg+xml
  • E. V. Maltsev Filatov Institute of Eye Diseases and Tissue Therapy of the National Academy of Medical Sciences of Ukraine image/svg+xml
  • O. V. Zborovska Filatov Institute of Eye Diseases and Tissue Therapy of the National Academy of Medical Sciences of Ukraine image/svg+xml https://orcid.org/0000-0003-2906-7367

DOI:

https://doi.org/10.31288/Ukr.j.ophthalmol.202648389

Keywords:

diabetic retinopathy, diabetes mellitus, retina, morphometry, neurodegeneration

Abstract

Purpose. To perform morphometric analysis of retinal structural components in rabbits in experimental diabetes mellitus (DM) in an attempt to digitize possible retinal neurodegenerative changes foe comparison with other species with induced DM.

Material and Methods: Stained hematoxylin and eosin histological sections from 19 eyes of 19 Chinchilla rabbits were retrospectively reviewed. Of the 19 eyes, 11 were from 11 rabbits at 16–17-week diabetes duration, and 4 were from 4 healthy rabbits. Total retinal thickness was measured in micrometers, and thicknesses of the following layers were measured in the neurosensory retina:  the photoreceptor layer (PRL), outer nuclear layer (ONL), outer plexiform layer (OPL), inner nuclear layer (INL), inner plexiform layer (IPL), and ganglion cell layer (GCL)/ nerve fiber layer (NFL). The numbers of nuclear rows in both nuclear layers were calculated visually. An eyepiece micrometer was used to perform retinal layer thickness measurements.

Results. Total retinal thickness (mean ± standard error of mean) was 110.6 ± 3.77 µm for healthy animals versus 111.0 ± 2.33 µm for diabetic animals; PRL thickness, 27.8 ± 2.11 µm versus 21.9 ± 1.30 µm; ONL thickness, 28.4 ± 0.97 µm versus 11.0 ±0.60 µm; OPL thickness, 8.1 ± 1.37 µm versus 27.8 ± 0.85 µm; INL thickness, 13.8 ± 0.99 µm versus 6.1 ± 0.61 µm; OPL thickness, 16.0 ± 1.05 µm  versus 18.3 ± 0.65 µm; and GCL/NFL thickness, 16.5 ± 1.04 µm versus 25.8 ± 0.64 µm, respectively. The number of nuclear rows in the ONL was 6.94 ± 0.17 for healthy animals versus 1.96 ± 0.10 for diabetic animals. The number of nuclear rows in the INL was 3.03 ± 0.09 for healthy animals versus 1.57 ± 0.05 for diabetic animals. Obviously, the retina of diabetic rabbits showed pronounced signs of neurodegeneration.

Conclusion. Microscopic pictures of retinal sections of and the estimated thicknesses of individual retinal layers and numbers of nuclear rows in the ONL and INL from, diabetic rabbits at 16–17-week diabetes duration indicate that the dithizone-induced diabetes rabbit model used may be considered suitable for histological (hematoxylin and eosin) evaluation of retinal degenerative changes.

 

Author Biographies

  • O. E. Dorokhova, Filatov Institute of Eye Diseases and Tissue Therapy of the National Academy of Medical Sciences of Ukraine

    Oleksandra E. Dorokhova, Cand Sc (Med) and Senior Researcher, Department of Ocular Inflammatory Disease, SI “The Filatov Institute of Eye Diseases and Tissue Therapy of the National Academy of Medical Sciences of Ukraine”, Odesa (Ukraine)

  • L. I. Samoilenko, Filatov Institute of Eye Diseases and Tissue Therapy of the National Academy of Medical Sciences of Ukraine

    Lyudmyla I. Samoilenko, Junior Researcher and Physician, Consultative Polyclinic, SI “The Filatov Institute of Eye Diseases and Tissue Therapy of the National Academy of Medical Sciences of Ukraine”, Odesa (Ukraine)

  • E. V. Maltsev, Filatov Institute of Eye Diseases and Tissue Therapy of the National Academy of Medical Sciences of Ukraine

    Eduard V. Maltsev, Dr Sc (Med), Professor and Chief Researcher, Pathomorphology and Electron Microscopy Laboratory, SI “The Filatov Institute of Eye Diseases and Tissue Therapy of the National Academy of Medical Sciences of Ukraine”, Odesa (Ukraine)

  • O. V. Zborovska, Filatov Institute of Eye Diseases and Tissue Therapy of the National Academy of Medical Sciences of Ukraine

    Oleksandra V. Zborovska, Dr Sc (Med), Professor and Acting Head, Department of Ocular Inflammatory Disease, and Deputy Research Director, SI “The Filatov Institute of Eye Diseases and Tissue Therapy of the National Academy of Medical Sciences of Ukraine”, Odesa (Ukraine)

References

Lovic D, Piperidou A, Zografou I, Grassos H, Pittaras A, Manolis A. The growing epidemic of diabetes mellitus. Curr Vasc Pharmacol. 2020;18(2):104-109.https://doi.org/10.2174/1570161117666190405165911

International Diabetes Federation. IDF Diabetes Atlas. 11th ed. [Internet]. Brussels: International Diabetes Federation; 2025. Available from: https://international-diabetes-federation.s3.eu-west-1.amazonaws.com/media/uploads/sites/3/2025/10/IDF_Diabetes_Atlas_11th_Edition_2025_WEB.pdf.

Barth T, Helbig H, Radeck V, Spital G, Faatz H. Diabetische Retinopathie: Epidemiologie, Stadien, Diagnostik, Screening und Therapie [Diabetic retinopathy: epidemiology, stages, diagnostics, screening and therapy]. Diabetologie (Berl). 2024;20(3):469-479. https://doi.org/10.1007/s11428-023-01133-1

Alifanov IS, Sakovych VM. [Prognostic risk factors for diabetic retinopathy in patients with type 2 diabetes mellitus]. Oftalmol Zh. 2022;(6):19-23.https://doi.org/10.31288/oftalmolzh202261923

Giyasova AO, Yangieva NR. Comparing the effectiveness of brolucizumab therapy alone versus that combined with subthreshold micropulse laser exposure in the treatment of diabetic macular edema. Oftalmol Zh. 2023;(2):16-20. https://doi.org/10.31288/oftalmolzh202321620

Teo ZL, Tham YC, Yu M, et al. Global Prevalence of Diabetic Retinopathy and Projection of Burden through 2045: Systematic Review and Meta-analysis. Ophthalmology. 2021;128(11):1580-1591. https://doi.org/10.1016/j.ophtha.2021.04.027

Hyung Cho, Alwassia AA, Regatieri CV, et al. Retinal neovascularization secondary to proliferative diabetic retinopathy characterized by spectral domain optical coherence tomography. Retina. 2013 Mar;33(3):542-547. https://doi.org/10.1097/IAE.0b013e3182753b6f

Wykoff CC, Yu HJ, Avery RL, et al. Retinal non-perfusion in diabetic retinopathy. Eye (Lond). 2022 Feb;36(2):249-256. https://doi.org/10.1038/s41433-021-01649-0

WalkerJ, Риков СА, Сук СА. и др. [Діабетична ретинопатія. Просто про складне]. Київ: ООО «Бизнес-логика», 2013. 320 с.

Мальцев Е, Зборовська ОВ, Дорохова ОЕ.[Фундаментальні аспекти розвитку і лікування діабетичної ретинопатії]. Одеса:Астропринт, 2018. -218

Nevska AO, Pohosian OA, Goncharuk KO, Sofyna DF, Chernenko OO, Tronko KM, et al. Detecting diabetic retinopathy using an artificial intelligence-based software platform: A pilot study. Oftalmol Zh. 2024;(1):27-32. https://doi.org/10.31288/oftalmolzh202412731

Rykov SO, Galytska YeP, Zhmuryk DV, et al. Association of the rs1927911 polymorphism of the TLR4 gene with diabetic retinopathy and diabetic macular edema in type 2 diabetes. Oftalmol Zh. 2024;(1):20-26. DOI: https://doi.org/10.31288/oftalmolzh202412026

Simó R, Hernández C. Neurodegeneration in the diabetic eye: new insights and therapeutic perspectives. Trends Endocrinol Metab. 2014 Jan;25(1):23-33.https://doi.org/10.1016/j.tem.2013.09.005

Antonetti DA, Silva PS, Stitt AW. Current understanding of the molecular and cellular pathology of diabetic retinopathy. Nat Rev Endocrinol. 2021 Apr;17(4):195-206.https://doi.org/10.1038/s41574-020-00451-4

Lynch SK, Abràmoff MD. Diabetic retinopathy is a neurodegenerative disorder. Vision Res. 2017 Oct;139:101-107. https://doi.org/10.1016/j.visres.2017.03.003

Ratra D, Nagarajan R, Dalan D, et al. Early structural and functional neurovascular changes in the retina in the prediabetic stage. Eye. 2021 Mar;35(3):858-867.https://doi.org/10.1038/s41433-020-0984-z

Barber AJ, Robinson WF, Jackson GR. Neurodegeneration in Diabetic Retinopathy. In: Tombran-Tink J, Barnstable C, Gardner T, editors. Visual Dysfunction in Diabetes. New York: Springer; 2012. p. 189-209. https://doi.org/10.1007/978-1-60761-150-9_12

Llorián-Salvador M, Cabeza-Fernández S, Gomez-Sanchez JA, et al. Glial cell alterations in diabetes-induced neurodegeneration. Cell Mol Life Sci. 2024 Jan 18;81(1):47.https://doi.org/10.1007/s00018-023-05024-y

Ola MS, Nawaz MI, Khan HA, Alhomida AS. Neurodegeneration and neuroprotection in diabetic retinopathy. Int J Mol Sci. 2013 Feb 1;14(2):2559-2572.https://doi.org/10.3390/ijms14022559

Sachdeva MM. Retinal Neurodegeneration in Diabetes: an Emerging Concept in Diabetic Retinopathy. Curr Diab Rep. 2021 Oct 5;21(11):65.https://doi.org/10.1007/s11892-021-01428-x

Ciprés M, Satue M, Melchor I, Gil-Arribas L, Vilades E, Garcia-Martin E. Retinal neurodegeneration in patients with type 2 diabetes mellitus without diabetic retinopathy. Arch Soc Esp Oftalmol (Engl Ed). 2022 Apr;97(4):205-218. https://doi.org/10.1016/j.oftale.2022.02.009

Silva-Viguera MC, García-Romera MC, López-Izquierdo I, De-Hita-Cantalejo C, Sánchez-González MC, Bautista-Llamas MJ. Contrast Sensitivity Assessment in Early Diagnosis of Diabetic Retinopathy: A Systematic Review. Semin Ophthalmol. 2023 May;38(4):319-332. https://doi.org/10.1080/08820538.2022.2116289

Dorokhova OE, Samoilenko LI, Maltsev EV, et al. Morphometric analysis of retinal structural components in Wistar rats in experimental diabetes mellitus. Oftalmol Zh. 2025;(1):41-46.https://doi.org/10.31288/oftalmolzh202514146

Dorokhova OE, Samoilenko LI, Maltsev EV, et al. Morphometric analysis of retinal structural components in СВА/С57 mice in experimental diabetes mellitus. Oftalmol Zh. 2025;(4):49-54.https://doi.org/10.31288/oftalmolzh20254954

Kern TS, Engerman RL. Comparison of retinal lesions in alloxan-diabetic rats and galactose-fed rats. Curr Eye Res. 1994 Nov;13(11):863-867. https://doi.org/10.3109/02713689409015087

Alder VA, Su EN, Yu DY, et al. Overview of studies on metabolic and vascular regulatory changes in early diabetic retinopathy. Aust N Z J Ophthalmol. 1998 May;26(2):141-148.https://doi.org/10.1111/j.1442-9071.1998.tb01530.x

Prince JH, editor. The rabbit in eye research. Springfield (IL): Charles C Thomas; 1964. 652 p.

Afarid M, Namvar E, Sanie-Jahromi F. Diabetic retinopathy and BDNF: a review on its molecular basis and clinical applications. J Ophthalmol. 2020 Jun 25;2020:1602739.https://doi.org/10.1155/2020/1602739

Eshaq RS, Wright WS, Harris NR. Oxygen delivery, consumption, and conversion to reactive oxygen species in experimental models of diabetic retinopathy. Redox Biol. 2014 Apr 24;2:661-666. https://doi.org/10.1016/j.redox.2014.04.006

Ishikawa M. Abnormalities in glutamate metabolism and excitotoxicity in the retinal diseases. Scientifica (Cairo). 2013;2013:528940. https://doi.org/10.1155/2013/528940

Nag TC. Pathogenic mechanisms contributing to the vulnerability of aging human photoreceptor cells. Eye (Lond). 2021 Oct;35(10):2917-2929. https://doi.org/10.1038/s41433-021-01602-1

Ambiya V, Kumar A, Bhavaraj VR, Sharma V, Sharma N. Study of inner retinal neurodegeneration in Diabetes Mellitus using spectral domain optical coherence tomography. Eur J Ophthalmol. 2022 Sep;32(5):3074-3081. https://doi.org/10.1177/11206721211048793

Borooah M, Nane YJ, Ekka J. Evaluation of thickness of retinal nerve fiber layer and ganglion cell layer with inner plexiform layer in patients without diabetic retinopathy and mild diabetic retinopathy in type 2 diabetes mellitus patients using spectral-domain optical coherence tomography. Int J Res Med Sci. 2018;6(7):2434-2439. https://doi.org/10.18203/2320-6012.ijrms20182831

Rajab HA, Baker NL, Hunt KJ, et al. The predictive role of markers of inflammation and endothelial dysfunction on the course of diabetic retinopathy in type 1 diabetes. J Diabetes Complications. 2015 Jan-Feb;29(1):108-114. https://doi.org/10.1016/j.jdiacomp.2014.08.004

Yu Y, Chen H, Su SB. Neuroinflammatory responses in diabetic retinopathy. J Neuroinflammation. 2015 Jul 29;12:141. https://doi.org/10.1186/s12974-015-0368-7

Rübsam A, Parikh S, Fort PE. Role of Inflammation in Diabetic Retinopathy. Int J Mol Sci. 2018 Apr 12;19(4):942. https://doi.org/10.3390/ijms19040942

Published

2026-08-31

Issue

Section

Experimental Studies

How to Cite

1.
Morphometric analysis of retinal structural components in rabbits in experimental diabetes mellitus. Ukr. j. ophthalmol. [Internet]. 2026 Aug. 31 [cited 2026 Sep. 1];(4):83-9. Available from: https://ua.ozhurnal.com/index.php/files/article/view/1025

Most read articles by the same author(s)

<< < 1 2