ophthalmologyОфтальмологияOphthalmology in Russia1816-50952500-0845Ophthalmology10.18008/1816-5095-2024-1-205-213ophthalmology-2312Research ArticleЭКСПЕРИМЕНТАЛЬНЫЕ ИССЛЕДОВАНИЯЕXPERIMENTAL STUDIESОценка возрастзависимых гистопатологических изменений, происходящих в слезной железе стареющих крыс WistarAssessment of Age-related Histopathological Changes Occurring in the Lacrimal Gland of Aging Wistar RatsНовиковаЮ. П.NovikovaYu. P.

Новикова Юлия Петровна — кандидат биологических наук, инженер

ул. Вавилова, 26, Москва, 119334

Novikova Yulia P. — PhD in Biology, engeneer

Vavilova str., 26, Moscow, 119334

novikovayulia@gmail.comhttps://orcid.org/0000-0003-0865-4730ГригорянЭ. Н.GrigoryanE. N.

Григорян Элеонора Норайровна — доктор биологических наук, главный научный сотрудник

ул. Вавилова, 26, Москва, 119334

Grigoryan Eleonora N. — PhD in Biology, leading research officer

Vavilova str., 26, Moscow, 119334

ФГБУН «Институт биологии развития им. Н.К. Кольцова» РАНРоссияN.K. Koltzov Institute of Developmental Biology, RASRussian Federation202401042024211205213Copyright © Новикова Ю.П., Григорян Э.Н., 20242024Новикова Ю.П., Григорян Э.Н.Novikova Y.P., Grigoryan E.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.ophthalmojournal.com/opht/article/view/2312Цель исследования

Цель исследования. Крысы Wistar часто используются в офтальмологических исследованиях и при тестировании веществ, обладающих терапевтическим действием. Состояние глаз этих животных, как и других млекопитающих и человека, в норме, при патологии и старении зависит от работы слезных желез. Целью данного исследования была разработка удобных подходов для определения возрастзависимых гистопатологических изменений в эксорбитальных слезных железах стареющих крыс.

Материал и методы

Материал и методы. Материалом исследования служили изолированные эксорбитальные слезные железы (ЭСЖ), полученные от крыс Wistar в возрасте 8 и 11 мес. Изменения в структуре ЭСЖ были оценены с помощью методов компьютерной обработки морфологических картин и количественной обработки данных.

Результаты

Результаты. Отражением функционирования и состояния ЭСЖ являются ее структурные изменения и прогрессирующее воспаление. В работе предложен простой способ оценки состояния ЭСЖ у стареющих крыс с использованием методов морфологии и компьютерных программ. С помощью предложенного подхода показано, что в период с 8 до 11 мес. постнатального развития у крыс Wistar происходят существенные возрастзависимые изменения. Они проявляются в прогрессе дистрофии паренхимы и прогрессирующей инфильтрации ткани клетками воспаления.

Заключение

Заключение. Предложенный в работе способ оценки состояния ЭСЖ может применяться в офтальмологических исследованиях, в частности при изучении развития синдрома сухого глаза и тестировании средств его терапии.

Purpose

Purpose. Wistar rats are often used in ophthalmological studies and in testing substances having therapeutic effects. The condition of the eyes of these animals, as well as other mammals, including humans, in the normal state, pathology, and aging, depends on the work of the lacrimal glands. The aim of this study was to develop convenient approaches for determining age-dependent histopathological changes in the exorbital lacrimal glands (ELGs) of aging rats.

Material and methods

Material and methods. Isolated ELGs obtained from Wistar rats aged of 8 and 11 months served as a material of the study. Changes in the structure of ELGs were evaluated using methods of computer analysis of morphological patterns and quantitative data processing.

Results

Results. The functioning and state of the ELGs are reflected in their dramatic structural changes and progressive inflammation. Our study proposes a simple way to assess the state of ELGs in aging rats using methods of morphology and computer programs. Using the proposed approach, it was shown that in the period from 8 to 11 months of postnatal development, significant age-related changes occur in aging rats. Changes manifest in the progress of parenchymal degeneration and progressive infiltration of the tissue by inflammatory cells.

Conclusions

Conclusions. The proposed method of ELG state’s evaluation can be used in ophthalmological studies, and in particular, when studying the development of “dry eye” syndrome and testing the means of its therapy.

млекопитающиеэкстраорбитальная слезная железавозрастзависимые изменениядистрофиявоспалениеmammalslacrimal glandage-related changesdegenerationinflammationРабота проводилась с использованием оборудования ЦКП ИБР им Н.К. Кольцова РАНThe work was carried out within the framework of the section of the State Assignment 2022 (No. 0088-2024-0014)ReferencesPaulsen F. Cell and molecular biology of human lacrimal gland and nasolacrimal duct mucins. Int. Rev. Cytol. 2006;249:229–279. doi: 10.1016/S00747696(06)49005-7.Paulsen F. Cell and molecular biology of human lacrimal gland and nasolacrimal duct mucins. Int. Rev. Cytol. 2006;249:229–279. doi: 10.1016/S00747696(06)49005-7.Hughes GK, Miszkiel KA. Imaging of the lacrimal gland. Semin Ultrasound CT MR. 2006;27(6):476–491. doi: 10.1053/j.sult.2006.09.002.Hughes GK, Miszkiel KA. Imaging of the lacrimal gland. Semin Ultrasound CT MR. 2006;27(6):476–491. doi: 10.1053/j.sult.2006.09.002.Schechter JE, Warren DW, Mircheff AK. A lacrimal gland is a lacrimal gland, but rodent’s and rabbit’s are not human. Ocul. Surf. 2010;8(3):111–134. doi: 10.1016/s1542-0124(12)70222-7.Schechter JE, Warren DW, Mircheff AK. A lacrimal gland is a lacrimal gland, but rodent’s and rabbit’s are not human. Ocul. Surf. 2010;8(3):111–134. doi: 10.1016/s1542-0124(12)70222-7.Гончарова OC, Манских ВН. Возрастные изменения в слезной железе крыс: яркая морфология, неясная природа. Онтогенез. 2014;45(5):289–298. doi: 10.7868/S047514501405005X.Gancharova OS, Manskikh VN. Age-related changes in the rat lacrimal gland: specific morphology and unknown nature. Ontogenesis. 2014;45(5):289–298 (In Russ.). doi: 10.1134/S1062360414050051.Hodges RR, Dartt DA. Regulatory pathways in lacrimal gland epithelium. Int. Rev. Cytol. 2003;231:129–196. doi: 10.1016/s0074-7696(03)31004-6.Hodges RR, Dartt DA. Regulatory pathways in lacrimal gland epithelium. Int. Rev. Cytol. 2003;231:129–196. doi: 10.1016/s0074-7696(03)31004-6.Dartt DA. Dysfunctional neural regulation of lacrimal gland secretion and its role in the pathogenesis of dry eye syndromes. Ocul. Surf. 2004;2(2):76–91. doi: 10.1016/s1542-0124(12)70146-5.Dartt DA. Dysfunctional neural regulation of lacrimal gland secretion and its role in the pathogenesis of dry eye syndromes. Ocul. Surf. 2004;2(2):76–91. doi: 10.1016/s1542-0124(12)70146-5.Warren DW. Hormonal influences on the lacrimal gland. Int. Ophthalmol. Clin. Winter. 1994;34(1):19–25. doi: 10.1097/00004397-199403410-00004.Warren DW. Hormonal influences on the lacrimal gland. Int. Ophthalmol. Clin. Winter. 1994;34(1):19–25. doi: 10.1097/00004397-199403410-00004.Sullivan DA, Wickham LA, Rocha EM. Influence of gender, sex steroid hormones, and the hypothalamic-pituitary axis on the structure and function of the lacrimal gland. Adv. Exp. Med. Biol. 1998;438:11–42. doi: 10.1007/978-1-4615-5359-5_2.Sullivan DA, Wickham LA, Rocha EM. Influence of gender, sex steroid hormones, and the hypothalamic-pituitary axis on the structure and function of the lacrimal gland. Adv. Exp. Med. Biol. 1998;438:11–42. doi: 10.1007/978-1-4615-5359-5_2.Skrzypecki J, Tomasz H, Ciepiaszuk K. Variability of dry eye disease following removal of lacrimal glands in rats. Adv. Exp. Med. Biol. 2019;1153:109–115. doi: 10.1007/5584_2019_348.Skrzypecki J, Tomasz H, Ciepiaszuk K. Variability of dry eye disease following removal of lacrimal glands in rats. Adv. Exp. Med. Biol. 2019;1153:109–115. doi: 10.1007/5584_2019_348.Zoukhri D, Fix A, Alroy J, Kublin CL. Mechanisms of murine lacrimal gland repair after experimentally induced inflammation. Invest. Ophthalmol. Vis. Sci. 2008;49(10):4399–4406. doi: 10.1167/iovs.08-1730.Zoukhri D, Fix A, Alroy J, Kublin CL. Mechanisms of murine lacrimal gland repair after experimentally induced inflammation. Invest. Ophthalmol. Vis. Sci. 2008;49(10):4399–4406. doi: 10.1167/iovs.08-1730.Zoukhri D. Mechanisms involved in injury and repair of the murine lacrimal gland: role of programmed cell death and mesenchymal stem cells. Ocul Surf. 2010;8(2):60–69. doi: 10.1016/s1542-0124(12)70070-8.Zoukhri D. Mechanisms involved in injury and repair of the murine lacrimal gland: role of programmed cell death and mesenchymal stem cells. Ocul Surf. 2010;8(2):60–69. doi: 10.1016/s1542-0124(12)70070-8.Stern ME, Pflugfelder SC. Inflammation in dry eye. Ocul. Surf. 2004;2:124–130. doi: 10.1016/s1542-0124(12)70148-9.Stern ME, Pflugfelder SC. Inflammation in dry eye. Ocul. Surf. 2004;2:124–130. doi: 10.1016/s1542-0124(12)70148-9.Stern ME, Pflugfelder SC. What We Have Learned from Animal Models of Dry. Eye. Int. Ophthalmol. Clin. 2017;57(2):109–118. doi: 10.1097/IIO.0000000000000169.Stern ME, Pflugfelder SC. What We Have Learned from Animal Models of Dry. Eye. Int. Ophthalmol. Clin. 2017;57(2):109–118. doi: 10.1097/IIO.0000000000000169.Ríos JD, Horikawa Y, Chen LL. Age-dependent alterations in mouse exorbital lacrimal gland structure, innervation and secretory response. Exp. Eye Res. 2005;80(4):477–491. doi: 10.1016/j.exer.2004.10.012.Ríos JD, Horikawa Y, Chen LL. Age-dependent alterations in mouse exorbital lacrimal gland structure, innervation and secretory response. Exp. Eye Res. 2005;80(4):477–491. doi: 10.1016/j.exer.2004.10.012.Rocha EM, Alves M, Rios JD, Dartt DA. The Aging Lacrimal Gland: Changes in Structure and Function. Ocul. Surf. 2008 Oct;6(4):162-74. doi: 10.1016/s15420124(12)70177-5Rocha EM, Alves M, Rios JD, Dartt DA. The Aging Lacrimal Gland: Changes in Structure and Function. Ocul. Surf. 2008 Oct;6(4):162-74. doi: 10.1016/s15420124(12)70177-5Draper CE, Adeghate EA, Singh J, Pallot DJ. Evidence to suggest morphological and physiological alterations of lacrimal gland acini with ageing. Exp. Eye Res. 1999;68(3):265–276. doi: 10.1006/exer.1998.0605.Draper CE, Adeghate EA, Singh J, Pallot DJ. Evidence to suggest morphological and physiological alterations of lacrimal gland acini with ageing. Exp. Eye Res. 1999;68(3):265–276. doi: 10.1006/exer.1998.0605.Draper CE, Singh J, Adeghate E. Effects of age on morphology, protein synthesis and secretagogue-evoked secretory responses in the rat lacrimal gland. Mol. Cell Biochem. 2003;248:7–16. doi: 10.1023/a:1024159529257.Draper CE, Singh J, Adeghate E. Effects of age on morphology, protein synthesis and secretagogue-evoked secretory responses in the rat lacrimal gland. Mol. Cell Biochem. 2003;248:7–16. doi: 10.1023/a:1024159529257.Vais VB, Vangeli IM, Bakeeva LE. Ultrastructural changes in ageing lacrimal gland in Wistar rats. Bull. Exp Biol Med. 2014;157(2):268–272. doi: 10.1007/s10517-014-2542-9.Vais VB, Vangeli IM, Bakeeva LE. Ultrastructural changes in ageing lacrimal gland in Wistar rats. Bull. Exp Biol Med. 2014;157(2):268–272. doi: 10.1007/s10517-014-2542-9.Obata H. Anatomy and histopathology of the human lacrimal gland. Cornea. 2006;25:S82–S89. doi: 10.1097/01.ico.0000247220.18295.d3.Obata H. Anatomy and histopathology of the human lacrimal gland. Cornea. 2006;25:S82–S89. doi: 10.1097/01.ico.0000247220.18295.d3.Obata H, Yamamoto S, Horiuchi H, Machinami R. Histopathologic study of human lacrimal gland. Statistical analysis with special reference to aging. Ophthalmology. 1995;102:678–686. doi: 10.1016/s0161-6420(95)30971-2.Obata H, Yamamoto S, Horiuchi H, Machinami R. Histopathologic study of human lacrimal gland. Statistical analysis with special reference to aging. Ophthalmology. 1995;102:678–686. doi: 10.1016/s0161-6420(95)30971-2.Huang W, Tourmouzis K, Perry H, Honkanen RA, Rigas B. Animal models of dry eye disease: Useful, varied and evolving (Review). Exp. Ther. Med. 2021;6:1394. doi: 10.3892/etm.2021.10830.Huang W, Tourmouzis K, Perry H, Honkanen RA, Rigas B. Animal models of dry eye disease: Useful, varied and evolving (Review). Exp. Ther. Med. 2021;6:1394. doi: 10.3892/etm.2021.10830.Wood JPM, Chidlow G, Halliday LA, Casson RJ, Selva D, Sun M. Histochemical Comparison of Human and Rat Lacrimal Glands: Implications for Bio-Engineering Studies. Transl. Vis. Sci. Technol. 2022;11(11):10. doi: 10.1167/tvst.11.11.10.Wood JPM, Chidlow G, Halliday LA, Casson RJ, Selva D, Sun M. Histochemical Comparison of Human and Rat Lacrimal Glands: Implications for Bio-Engineering Studies. Transl. Vis. Sci. Technol. 2022;11(11):10. doi: 10.1167/tvst.11.11.10.Новикова ЮП, Григорян ЭН. Ранее появление признаков старения в ретинальном пигментном эпителии у молодых крыс альбиносов. Онтогенез. 2020;51(6):440–449. Novikova YuP, Grigoryan EN. Early Appearance of Aging Signs in Retinal Pigment Epithelium in Young Albino Rats. Ontogenesis. 2020;51(6):440–449 (In Russ.). doi: 10.31857/S0475145020060063.Новикова ЮП, Григорян ЭН. Ранее появление признаков старения в ретинальном пигментном эпителии у молодых крыс альбиносов. Онтогенез. 2020;51(6):440–449. Novikova YuP, Grigoryan EN. Early Appearance of Aging Signs in Retinal Pigment Epithelium in Young Albino Rats. Ontogenesis. 2020;51(6):440–449 (In Russ.). doi: 10.31857/S0475145020060063.Eksioglu U, Atilgan HI, Yakin M. Antioxidant effects of vitamin D on lacrimal glands against high dose radioiodine-associated damage in an animal model. Cutan. Ocul. Toxicol. 2019;38(1):18–24. doi: 10.1080/15569527.2018.1498507.Eksioglu U, Atilgan HI, Yakin M. Antioxidant effects of vitamin D on lacrimal glands against high dose radioiodine-associated damage in an animal model. Cutan. Ocul. Toxicol. 2019;38(1):18–24. doi: 10.1080/15569527.2018.1498507.Koca G, Singar E, Akbulut A. The Effect of Resveratrol on Radioiodine Therapy-Associated Lacrimal Gland Damage. Curr. Eye Res. 2021;46(3):398–407. doi: 10.1080/02713683.2020.1803920.Koca G, Singar E, Akbulut A. The Effect of Resveratrol on Radioiodine TherapyAssociated Lacrimal Gland Damage. Curr. Eye Res. 2021;46(3):398–407. doi: 10.1080/02713683.2020.1803920.Mecum NE, Cyr D, Malon J, Demers D, Cao L, Meng ID. Evaluation of Corneal Damage After Lacrimal Gland Excision in Male and Female Mice. Invest. Ophthalmol. Vis. Sci. 2019;60(10): 3264–3274. doi: 10.1167/iovs.18-26457.Mecum NE, Cyr D, Malon J, Demers D, Cao L, Meng ID. Evaluation of Corneal Damage After Lacrimal Gland Excision in Male and Female Mice. Invest. Ophthalmol. Vis. Sci. 2019;60(10): 3264–3274. doi: 10.1167/iovs.18-26457.Draper CE, Adeghate E, Lawrence PA. Age-related changes in morphology and secretory responses of male rat lacrimal gland. J. Auton. Nerv. Syst. 1998;69:173–183. doi: 10.1016/s0165-1838(98)00026-5.Draper CE, Adeghate E, Lawrence PA. Age-related changes in morphology and secretory responses of male rat lacrimal gland. J. Auton. Nerv. Syst. 1998;69:173–183. doi: 10.1016/s0165-1838(98)00026-5.Fox R. Sjögren’s syndrome. Lancet. 2005;366(9482):321–331. doi: 10.1016/S01406736(05)66990-5.Fox R. Sjögren’s syndrome. Lancet. 2005;366(9482):321–331. doi: 10.1016/S01406736(05)66990-5.Mathers WD. Why the eye becomes dry: a cornea and lacrimal gland feedback model. CLAO J. 2000;26(3):159–165.Mathers WD. Why the eye becomes dry: a cornea and lacrimal gland feedback model. CLAO J. 2000;26(3):159–165.Knop E, Knop N, Brewitt H. Dry eye disease as a complex dysregulation of the functional anatomy of the ocular surface. New concepts for understanding dry eye disease. Ophthalmologe. 2003;100(11):917–928. doi: 10.1007/s00347-003-0935-7.Knop E, Knop N, Brewitt H. Dry eye disease as a complex dysregulation of the functional anatomy of the ocular surface. New concepts for understanding dry eye disease. Ophthalmologe. 2003;100(11):917–928. doi: 10.1007/s00347-003-0935-7.Yamaguchi T. Inflammatory Response in Dry Eye. Invest. Ophthalmol. Vis. Sci. 2018;59:DES192–199. doi: 10.1167/iovs.17-23651.Yamaguchi T. Inflammatory Response in Dry Eye. Invest. Ophthalmol. Vis. Sci. 2018;59:DES192–199. doi: 10.1167/iovs.17-23651.Batista TM, Tomiyoshi LM, Dias AC. Age-dependent changes in rat lacrimal gland anti-oxidant and vesicular related protein expression profiles. Mol. Vis. 2012;18:194–202.Batista TM, Tomiyoshi LM, Dias AC. Age-dependent changes in rat lacrimal gland anti-oxidant and vesicular related protein expression profiles. Mol. Vis. 2012;18:194–202.Chistyakov DV, Gancharova OS, Baksheeva VE. Inflammation in Dry Eye Syndrome: Identification and Targeting of Oxylipin-Mediated Mechanisms. Biomedicines. 2020;8:344. doi: 10.3390/biomedicines8090344.Chistyakov DV, Gancharova OS, Baksheeva VE. Inflammation in Dry Eye Syndrome: Identification and Targeting of Oxylipin-Mediated Mechanisms. Biomedicines. 2020;8:344. doi: 10.3390/biomedicines8090344.Souza RG, Yu Z, Hernandez H. Modulation of Oxidative Stress and Inflammation in the Aged Lacrimal Gland. Am. J. Pathol. 2021;191(2):294–308. doi: 10.1016/j.ajpath.2020.10.013.Souza RG, Yu Z, Hernandez H. Modulation of Oxidative Stress and Inflammation in the Aged Lacrimal Gland. Am. J. Pathol. 2021;191(2):294–308. doi: 10.1016/j.ajpath.2020.10.013.Grønskov K., Ek. J, Brondum-Nielsen K. Oculocutaneous albinism. Orphanet. J. Rare Dis. 2007;2:43–53. doi: 10.1186/1750-1172-2-43.Grønskov K., Ek. J, Brondum-Nielsen K. Oculocutaneous albinism. Orphanet. J. Rare Dis. 2007;2:43–53. doi: 10.1186/1750-1172-2-43.Summers CG. Albinism: Classification, clinical characteristics, and recent findings. Optom. Vis. Sci. 2009;86:659–662. doi: 10.1097/OPX.0b013e3181a5254c.Summers CG. Albinism: Classification, clinical characteristics, and recent findings. Optom. Vis. Sci. 2009;86:659–662. doi: 10.1097/OPX.0b013e3181a5254c.

The authors declare that there are no conflicts of interest present.