Induction of the development of vitreous environments of the human eye - Студенческий научный форум

XIII Международная студенческая научная конференция Студенческий научный форум - 2021

Induction of the development of vitreous environments of the human eye

Можилевская Е.С. 1, Ковалева И.В. 1, Бессонов Е.А. 1, Рева Г.В. 1
Текст работы размещён без изображений и формул.
Полная версия работы доступна во вкладке "Файлы работы" в формате PDF

Relevance: In order to better understand in vivo the numerous pathways and mechanisms leading to the pathogenesis of diabetic retiropathy and its complications, such as diabetic macular edema, to create the potential for more individual targeted treatment, it is necessary to study cellular interactions in the system of structures of the developing eye during human ontogenesis. Persistent hyperglycemia leads to the activation of many cellular pathways involved in the pathogenesis of DR, resulting in increased inflammation, oxidative stress, and vascular dysfunction [1, 2, 3]. DR, however, there is growing evidence that both inflammation and neurodegeneration occur in human diabetes even before clinical signs of DR develop [4, 5, 6].Despite the presence of refractive lenses in the complex and compound eyes of many invertebrates, relatively little is known about their crystallins [7, 8, 9]. The revealed numerous refractive structures, which have developed in the eyes of invertebrates, noticeably contrast with the limited information on their protein composition, which indicates its insufficient knowledge [10, 11, 12]. One of the first signs of inflammation in diabetes is the activation of retinal glial cells (RGC), which, with the appearance of inflammatory mediators, growth factors in the retinal layers, represent an in vivo marker of microglial activation accompanied by early loss of nerve cells, confirmed the hypothesis that neurodegeneration occurs at an early stage in both type 1 and type 2 diabetes [13, 14]. However, these mechanisms can be understood only on the basis of exhaustive ideas about the mechanisms of development of the human eye and the involution of its temporal structures.

Purpose of the study: Explore induction of the development of transparent environments of the human eye.

Material and methods: Using the material of 15 eyes of human embryos and fetuses, the time and localization of S100B positive cells in the transparent media of the eye were established by the method of immune histochemistry. The preparations are stained by the classical method with hematoxylin and eosin. Langerhans cells were detected by immunohistochemical method followed by analysis on a microscope Olympus-Bх-52.

Research results and their discussion. The development of eye structures was studied to clarify the role of neuroglial migrants from the wall of the optic cup and ectomesenchyme located between the cerebral vesicle and the ectoderm of the head end of the embryo in the tissue organization of the vitreous body, lens and cornea. Using the material of 15 human embryos and fetuses by the method of immune histochemistry, the timing and localization of S100B positive cells in the transparent media of the eye, migrants not only from the ectomesenchyme surrounding the forming optic cup on the posterolateral surfaces, but also from the neural retina, were established. At week 5, not only active migration of precursor neuroglial cells, which form a matrix for the formation of the internal bipolar and ganglionic layers, occurs from the inner wall of the optic cup, but also its eviction outside the optic cup wall in the direction of the vitreous body, lens and cornea (fig. 1, 2).

Figure 1 - Eye of a human embryo 6 weeks old (weight 25 g).

Staining with hematoxylin and eosin. Magnification x100. c-retina, x-lens, хэ - lens epithelium; 1-primary ocular vesicle; 2 - vitreous

Figure 2 - Human fetal eye 10 weeks old. Staining with hematoxylin and eosin. Microphoto.

Magnification x 100.

Ectomesenchyme, which is the basis for the formation of a common rudiment for the vascular and fibrous membranes of the eye, serves as the main source of scleral development. Differentiation of ectomesenchymocytes goes in the direction of fibroblasts synthesizing connective tissue of the opaque sclera, in which active vasculogenesis occurs.

Neuroglial migrants from the retina populate the forming structures of the transparent media of the human eye and differentiate into a special type of fibroblasts that, like the neuroglia of the retina and visual cortex, are capable of secreting an extracellular matrix consisting of crystallins and a basic substance that inhibits the germination of blood vessels. Involution of the vascular capsule of the lens and the hyaloid basin of the vitreous body is associated with this process. Differentiation of neuroglia inhabiting the transparent media of the eye and the outer neuronal retinal layer occurs earlier than macroglia in the bipolar and ganglionic layers, and the common origin of neuroglial derivatives explains the absence of their own blood vessels in the photoreceptor layer of the retina and transparent media of the human eye.

According to G.V. Reva, I.V. Kovaleva. (2014), the physically transparent cornea, lens and vitreous humor are opaque from a histophysiological point of view and, therefore, cannot directly transmit light to the retina [1]. The developing lens has 2 sources of development: ectoderm, as a source for the capsular epithelium and neuroglial, for the stroma. Crystallins make up 80-90% of the water-soluble proteins of the clear lens. Crystallin recruitment occurs through changes in gene regulation leading to high lens expression. These diverse proteins are responsible for the optical properties of the lens and have been derived from metabolic enzymes and stress proteins. The development of retinal vessels is a complex process that has not yet been fully understood. Most of the research in this area has focused on astrocytes and the structures they form in the inner wall of the optic cup, a period that precedes endothelial cells and angiogenesis in the retina. However, in humans and dogs, astrocyte migration follows the development of blood vessels, suggesting that other cell types are able to induce this process. One of these cell types is the ganglion cell, which differentiates to form blood vessels and is located adjacent to the primary vascular plexus of the retina. The authors' data indicate that neuroglial migrants from the retina, as a result of differentiation, then specialize in stromal fibroblasts of the base of the cornea, as well as cell differentions of the vitreous body of the human organ of vision. A single source of transparent structures of the eye is explained and confirmed by the fact that the cornea, lens, vitreous body, neuroglia of the retina and brain contain proteins that are specific to all these structures - crystallins [1]. A known 59 kDa crystallin polypeptide previously observed in octopuses is omega-crystallin and has been identified as aldehyde dehydrogenase. Based on the notion that the same transcription factors (for example, Pax-6, retinoic acid receptors, maf, Sox, AP-1, CREB) regulate different crystallin bead genes, it can be assumed that the common features of lens-specific expression played a key role in attracting a variety of multifunctional proteins such as crystallins. Cellular interactions and histophysiology of fibroblasts of the transparent media of the eye explains the identity of the functions of crystallin secretion. Physiochemical properties and characteristics of crystallins prevent diffusion of light and direct it in one channel. The authors' data on neuroglial sources of origin of the lens stroma suggest that lens cells may act like Müllerian glia in the regulation of transformed energy flow. Consequently, all structures of the transparent media of the human eye, including the fibers and stromal cells of the cornea, lens, vitreous humor and retinal glia, have the ability to function as components of the universal conductive system of light perception, converting it into another type of energy (presumably into electromagnetic waves or some motor impulse), and only then sending it to the photoreceptors. As a result, we have one-way light conduction with the help of stromal cells of the vitreous structures of the human eye and at the same time the lack of the ability of the retina to identify these cells. That is why the cells located in front of the retina are invisible to photoreceptor cells in normal physiological regeneration. Only those structures that can be identified by this unique conduction system are visible.

Conclusion. It is known that Müller cells are slightly different in the GFAP retina in the absence of pathology and in diseases of the retina accompanied by detachment. The bases of these cells can be structurally strengthened by the cytoskeleton through intermediate filaments; our data also indicate a critical role for these proteins in the response of Müller cells to retinal detachment and participation in subretinal gliosis. The transparent media of the eye are derived structures of the neuroglial migrants of the human retina. The ability to secrete crystallins unites them into one functional group with the neuroglia of the visual cortex and retina, and also serves as evidence of the influence of the general signaling system in the process of differentiation.

The leading inducers in the development of transparent media of the human eye is the migration of neuroglial cells with subsequent differentiation into structures with the secretion of crystallins that inhibit the vascularization of transparent media of the organ of vision.

The study was financially supported by the International Medical Research and Education Center (Vladivostok, Russia).


1.Reva GV, Kovaleva IV, Reva IV, Yamamoto T, Novikov AS, Lomakin AV, Kulikova ES. Role of the neuroglia of human ocular transparent structures in the visual perception concepts. Bull Exp Biol Med. 2013 Feb;154(4):515-20. English, Russian. doi: 10.1007/s10517-013-1991-x.

2. Luna G, Keeley PW, Reese BE, Linberg KA, Lewis GP, Fisher SK. Astrocyte structural reactivity and plasticity in models of retinal detachment.//Exp Eye Res. 2016 Sep;150:4-21. doi: 10.1016/j.exer.2016.03.027.

3.Salazar-Quiñones L, Arcos-Villegas G, Valverde-Megías A, Flores-Moreno I, Méndez-Fernández R, Díaz-Valle D. Vitreous haemorrhage a rare manifestation of retinal astrocytic hamartoma: a paediatric case report. Arch Soc Esp Oftalmol. 2019 Sep;94(9):449-452. English, Spanish. doi: 10.1016/j.oftal.2019.04.012. 

4.Vishwakarma S, Gupta RK, Jakati S, Tyagi M, Pappuru RR, Reddig K, Hendricks G, Volkert MR, Khanna H, Chhablani J, Kaur I. Molecular Assessment of Epiretinal Membrane: Activated Microglia, Oxidative Stress and Inflammation.//Antioxidants (Basel). 2020 Jul 23;9(8):654. doi: 10.3390/antiox9080654. Pablo Y, Marasek P, Pozo-Rodrigálvarez A, Wilhelmsson U, Inagaki M, Pekna M, Pekny M. Vimentin Phosphorylation Is Required for Normal Cell Division of Immature Astrocytes.//Cells. 2019 Sep 1;8(9):1016. doi: 10.3390/cells8091016.

6.Josifovska N, Lumi X, Szatmari-Tóth M, Kristóf E, Russell G, Nagymihály R, Anisimova N, Malyugin B, Kolko M, Ivastinović D, Petrovski G. Clinical and molecular markers in retinal detachment-From hyperreflective points to stem cells and inflammation.//PLoS One. 2019 Jun 11;14(6):e0217548. doi: 10.1371/journal.pone.0217548.

7.Tomarev SI, Zinovieva RD, Guo K, Piatigorsky J. Squid glutathione S-transferase. Relationships with other glutathione S-transferases and S-crystallins of cephalopods.//J Biol Chem. 1993 Feb 25;268(6):4534-42.

8. Tomarev SI, Zinovieva RD, Piatigorsky J. Characterization of squid crystallin genes. Comparison with mammalian glutathione S-transferase genes.//J Biol Chem. 1992 Apr 25;267(12):8604-12.

9.Piatigorsky J. Crystallin genes: specialization by changes in gene regulation may precede gene duplication.//J Struct Funct Genomics. 2003;3(1-4):131-7.

10.Nakazawa T, Takeda M, Lewis GP, Cho KS, Jiao J, Wilhelmsson U, Fisher SK, Pekny M, Chen DF, Miller JW. Attenuated glial reactions and photoreceptor degeneration after retinal detachment in mice deficient in glial fibrillary acidic protein and vimentin.//Invest Ophthalmol Vis Sci. 2007 Jun;48(6):2760-8. doi: 10.1167/iovs.06-1398.

11.Verardo MR, Lewis GP, Takeda M, Linberg KA, Byun J, Luna G, Wilhelmsson U, Pekny M, Chen DF, Fisher SK. Abnormal reactivity of muller cells after retinal detachment in mice deficient in GFAP and vimentin.//Invest Ophthalmol Vis Sci. 2008 Aug;49(8):3659-65. doi: 10.1167/iovs.07-1474.

12.Edwards MM, McLeod DS, Li R, Grebe R, Bhutto I, Mu X, Lutty GA. The deletion of Math5 disrupts retinal blood vessel and glial development in mice. Exp Eye Res. 2012 Mar;96(1):147-56. doi: 10.1016/j.exer.2011.12.005.

13.Tomarev SI, Piatigorsky J. Lens crystallins of invertebrates--diversity and recruitment from detoxification enzymes and novel proteins.//Eur J Biochem. 1996 Feb 1;235(3):449-65. doi: 10.1111/j.1432-1033.1996.00449.x.

14.Zinovieva RD, Tomarev SI, Piatigorsky J. Aldehyde dehydrogenase-derived omega-crystallins of squid and octopus. Specialization for lens expression.//J Biol Chem. 1993 May 25;268(15):11449-55.

Просмотров работы: 66