O. V. Nedzvetska 1, U. A. Pastukh 1, E. V. Kihtenko 2, I. V. Pastukh 3, N. N. Sotnik 4, N. A. Goncharova 3, O. V. Kuzmina de Gutarra 1
1 Kharkiv Medical Academy of Post-Graduate Education; Kharkiv (Ukraine)
2 Kharkiv National Medical University; Kharkiv (Ukraine)
3 V. N. Karazin Kharkiv National University; Kharkiv (Ukraine)
4 SI "V. Danilevsky Institute for Endocrine Pathology Problems of the NAMS of Ukraine"; Kharkiv (Ukraine)
TO CITE THIS ARTICLE: Nedzvetska OV, Pastukh UA, Kihtenko EV, Pastukh IV, Sotnik NN, Goncharova NA, Kuzmina de Gutarra OV. Morphological and functional changes in the rabbit iris and ciliary body in experimental hypopinealism. J.ophthalmol.(Ukraine).2022;2:42-7. http://doi.org/10.31288/oftalmolzh202224247
Background: Previous morphological studies have found degenerative retinal abnormalities in experimental hypopinealism. It is important to determine the morphology and function of the iris and ciliary body in prolonged pineal gland dysfunction with melatonin deficiency.
Purpose: To determine the morphology and function of the iris and ciliary body in rabbits maintained under conditions of prolonged around-the-clock illumination leading to hypopinealism and melatonin deficiency.
Material and Methods: Fifty five adult rabbits (110 eyes) were used in this experimental study. Animals were divided into two groups, an experimental group of 32 animals maintained under conditions of around-the-clock illumination to induce functional hypopinealism, and a control group of 23 animals maintained under natural day/night cycle conditions. Both groups were subdivided into 5 subgroups based on the duration of the experiment: 1-2 months, 3-5 months, 8-12 months, 18-19 months, and) 26-28 months. Blood melatonin levels were assessed by an enzyme-linked immunosorbent assay. A comprehensive morphological study of rabbit iris and ciliary body specimens was conducted.
Results. Blood melatonin level at night time in the experimental group was almost six-fold lower than blood melatonin level in the control group. In animals maintained under conditions of around-the-clock illumination, marked circulatory abnormalities with markedly dilated and hyperemic vessels were observed in the iris and ciliary body at time points until 12 months. In addition, at 12 to 28 months, iris and ciliary body vascular circulatory abnormalities appeared to be changed by sclerotic abnormalities. In animals exposed to around-the-clock illumination, vascular sclerotic changes appeared substantially earlier, and were much more marked, than in control animals. The mean vascular wall thickness (VWT) in iris and ciliary body specimens for the experimental group was 1.5-fold higher than that for the control group (177.5 ± 7.3×10-6 m vs 101.9 ± 4.4×10-6; р < 0.05) at 18 to 19 months, and twice higher than that for the control group (217.4 ± 8.7×10-6 m vs 107.2 ± 5.2 ×10-6 m) at 26 to 28 months. The like newly formed rough bundles of collagen fibers found in an analogue of the Schlemm canal may exert a very negative effect on hydrodynamics of the eye.
Keywords: ciliary body, iris, around-the-clock illumination, hypopinealism, melatonin, morphological and functional changes
Disclaimer: The authors state that the thoughts expressed in this article are their own and not the official positions of the institutions
Sources of support: none
Conflict of Interest Declaration: the authors declare that there are no real or potential conflicts of interest (financial, personal, professional, or other interests) that could affect the content or conclusions of this manuscript.
1.Brainard GC, Hanifin JP, Greeson JM, et al. Action spectrum for melatonin regulation in humans: evidence for a novel circadian photoreceptor. J Neurosci. 2001 Aug 15;21(16):6405-12.
2.Gooley JJ , Rajaratnam SM, Brainard GC, et al. Spectral responses of the human circadian system depend on the irradiance and duration of exposure to light. Sci Transl Med. 2010 May 12;2(31):31ra33.
3.Korf HW, Schomerus C, Stehle JH. The pineal organ, its hormone melatonin, and the photoneuroendocrine system. Adv Anat Embryol Cell Biol. 1998; 146:1-100.
4.Moore RY. Organization and function of a central nervous system circadian oscillator: the suprachiasmatic hypothalamic nucleus. Fed Proc. 1983 Aug;42(11):2783-9.
5.Ruby NF, Brennan TJ, Xie X, et al. Role of melanopsin in circadian responses to light. Science. 2002 Dec 13;298(5601):2211-3.
6.Wetterberg L. Light and biological rhythms. J Intern Med. 1994 Jan;235(1):5-19.
7.Bondarenko LA, Gubina-Vakulik GI, Sotnik NN. [Effects of constant light on the rabbit’s circadian melatonin rhythm and pineal gland structures]. Problemy endocrinnoi patologii. 2005;4:38-45. Russian.
8.Gubina-Vakulik GI, Bondarenko LA, Sotnik NN. [Prolonged around-the-clock illumination as a factor of accelerated aging of the pineal gland]. Uspekhi gerontologii. 2007; 20(1): 92-5. Russian.
9.Alkozi HA, Wang X, Perez de Lara M, Pintor J. Presence of melanopsin in human crystalline lens epithelial cells and its role in melatonin synthesis. Exp Eye Res. 2017; 154:168–76.
10.Cahill GM, Besharse JC. Light‐sensitive melatonin synthesis by Xenopus photoreceptors after destruction of the inner retina. Vis Neurosci. 1992; 8: 487–90.
11.Hamm HE, Menaker M. Retinal rhythms in chicks: circadian variation in melatonin and serotonin N‐acetyltransferase activity. Proc Natl Acad Sci USA. 1980 Aug;77(8):4998-5002.
12.Iuvone PM, Tosini G, Pozdeyev N, et al. Circadian clocks, clock networks, arylalkylamine N‐acetyltransferase, and melatonin in the retina. Prog Retin Eye Res. 2005; 2005 Jul;24(4):433-56.
13.Martin XD, Malina HZ, Brennan MC, et al. The ciliary body - the third organ found to synthesize indoleamines in humans. Eur J Ophthalmol. 1992;2:67–72.
14.Pescosolido N, Gatto V, Stefanucci A, Rusciano D. Oral treatment with the melatonin agonist agomelatine lowers the intraocular pressure of glaucoma patients. Ophthalmic Physiol Opt. 2015 Mar;35(2):201-5.
15.Nedzvetskaya OV, Kolot AV, Bondarenko LA. [Investigating retinal morphological changes in experimental hypopinealism]. Oftalmologiiaa. Vostochnaia Evropa. 2015; 2 (25): 35-40. Russian.
16.Matviienko AV, Stepanova LV. [Guidelines on preclinical morphological studies in preclinical medication trials]. Kyiv: State Pharmacological Center at the Ministry of Health of Ukraine; 2001. Ukrainian.
17.Lillie RD. [Histopathologic technic and practical histochemistry]. Moscow: Mir; 1969. Russian.
18.Sarkisov DS, Perova IuL, editors. [Microscopic technique: a manual]. Moscow: Meditsina; 1996. Russian.
19.Lapach SN, Chubenko AV, Babich PN. [Statistical methods in medical and biological studies using Excel]. 2nd ed. Kyiv: Morion; 2007. Russian.
20.Avtandilov G.G. [Basics of quantitative pathological anatomy]. Moscow: Meditsina; 2002. Russian.
21.Sergiienko VI., Bondareva IB. [Mathematical statistics in clinical studies] Moscow: Geotar Meditsina; 2000. Russian.
22.Lemaigre-Voreaux P. Melatonine et Lumiere. Lux. 1986; 139:183-97.