Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Dec 15, 2018; 9(12): 239-251
Published online Dec 15, 2018. doi: 10.4239/wjd.v9.i12.239
Pathological changes in the cellular structures of retina and choroidea in the early stages of alloxan-induced diabetes
Irina Danilova, Svetlana Medvedeva, Svetlana Shmakova, Margarita Chereshneva, Alexey Sarapultsev, Petr Sarapultsev
Irina Danilova, Svetlana Medvedeva, Svetlana Shmakova, Department of Biology and Fundamental Medicine, Institute of Natural Sciences and Mathematics, Ural Federal University Named After the First Pres. of Russia B.N. Yeltsin, Ekaterinburg 620002, Russia
Irina Danilova, Svetlana Medvedeva, Svetlana Shmakova, Laboratory of Morphology and Biochemistry, Institute of Immunology and Physiology, Ural Division of Russian Academy of Sciences, Ekaterinburg 620049, Russia
Margarita Chereshneva, Laboratory of Immunophysiology and Immunopharmacology, Institute of Immunology and Physiology, Ural Division of Russian Academy of Sciences, Ekaterinburg 620049, Russia
Alexey Sarapultsev, Petr Sarapultsev, Institute of Chemical Engineering, Ural Federal University Named After the First Pres. of Russia B.N. Yeltsin, Ekaterinburg 620002, Russia
Alexey Sarapultsev, Petr Sarapultsev, Laboratory of Immunophatophysiology, Institute of Immunology and Physiology, Ural Division of Russian Academy of Sciences, Ekaterinburg 620049, Russia
Author contributions: Danilova I, Chereshneva M, Sarapultsev P, and Sarapultsev A contributed to the conception of the manuscript, design of experiments, and analysis and interpretation of the data, and wrote the manuscript; Danilova I, Medvedeva S, Shmakova S, and Sarapultsev A performed the experiments, analyzed the data, and wrote the manuscript; all authors have commented on the initial and final drafts of the manuscript and are responsible for approval of the final version of the manuscript in all aspects.
Supported by the Russian Science Foundation, No. 16-15-00039.
Institutional review board statement: This study protocol was reviewed and approved by the Institutional Review Board of Institute of Immunology and Physiology of Ural Branch of RAS, Ekaterinburg, Russia.
Institutional animal care and use committee statement: All institutional and national guidelines for the care and use of laboratory animals were followed. All experimental procedures with the animals were approved by the Institute of Animal Care and Use Committee at the Institute of Immunology and Physiology of the Ural Division of RAS (diab-1-04-2016).
Conflict-of-interest statement: The authors declare that there is no conflict of interest regarding the publication of this paper.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author to: Alexey Sarapultsev, MD, PhD, Senior Researcher, Laboratory of Immunophatophysiology, Institute of Immunology and Physiology, Ural Division of Russian Academy of Sciences, 106 Pervomayskaya Street, Ekaterinburg 620049, Russia. a.sarapultsev@gmail.com
Telephone: +7-343-3740070 Fax: +7-343-3740070
Received: June 26, 2018
Peer-review started: June 26, 2018
First decision: July 19, 2018
Revised: September 1, 2018
Accepted: November 2, 2018
Article in press: November 3, 2018
Published online: December 15, 2018
ARTICLE HIGHLIGHTS
Research background

Diabetic retinopathy (DR) is a disease commonly associated with diabetes complications. It is known as one of the primary causes of visual impairment and blindness globally. More recent discoveries have shown that indicators of inflammation, altered vascular permeability, and increased production of inflammatory mediators occurs in the retina after 1-6 mo of the presence of diabetes. However, most of therapeutic approaches being developed do not address the early and potentially reversible failure of retinal perfusion.

Research motivation

Better understanding of the temporal sequence and stages of pathological disturbances of DR development is of scientific value, as it might contribute to improvements to current methods or even the development of new methods of diagnosis and treatment of the early and potentially reversible failure of retinal perfusion.

Research objectives

We have investigated the temporal sequence of pathological changes in the cellular structures of retina and choroidea in a rat model of alloxan-induced diabetes in the early stages of disease.

Research methods

Alloxan accumulates in pancreatic cells, resulting in selective β-cell necrosis and diabetes. Experimental diabetes was modeled by three intraperitoneal injections (10 mg/100 g of weight) of an alloxan solution dissolved in physiological saline at 1-d intervals (total dose of alloxan 30 mg/100 g). The 30th and 60th days from the final alloxan injection were chosen as the endpoints of the experiment. Biochemical and enzyme immunoassay were performed. Furthermore, histological, immunohistochemical, and electron microscopy methods were employed to evaluate the rat’s eye slices. Similarly, light microscopy and morphometric analyses of slides were also conducted.

Research results

In the present study, the alloxan-induced diabetes model demonstrated that in the early stages of the disease, diabetic alterations in the structures of the retina and choroid are present, and these alterations progress with time. In the retina, DR manifest itself as a partial destruction of the structural-functional elements, namely, photoreceptors and are accompanied by a stromal reaction in the form of the development of interstitial edema and a reduction in the thickness of the retina due to photoreceptor destruction. The reduction in the number of blood vessels of the choroid, melanocytes, and pigment cells along with an increase in the number of macrophages were also observed at early stages of the disease.

Research conclusions

The results of this study provide evidence that DR manifests itself at the early stages of diabetes. The starting point in the development of DR involves the early reduction in the number of melanocytes of the choroidea and the destruction of the retinal pigment epithelium, which are the primary components of the hematoretinal barrier.

Research perspectives

Further studies that estimated vascular endothelial growth factor, prostate-derived Ets transcription factor, cytokines, NO, and antioxidants and correlated them with blood glucose levels and changes in the retina in various experimental models and at different time periods will contribute to the improvements and the development of new methods of diagnosis and treatment of DR.