Abstract
Retinal pigment epithelium (RPE), whose main functions are to participate directly in light perception and ensure the trophic and functioning of the retina, is a traditional subject of numerous studies. A significant part of them is biomedical and is aimed at identifying the causes of aging and degeneration of RPE, which are, in turn, associated with several serious retinal diseases that lead to the loss of the eyesight. Rodents, in particular, the albino Wistar rats, are often used as the object of these studies. The work is aimed at identifying signs of aging in the RPE in young (from 2 weeks up to 2 months) albino rats. Using the methods of fluorescence analysis and Schmorl staining, the accumulation of the “aging pigment” lipofuscin in the isolated layer of RPE, as well as a high content of polyploid binuclear cells to mononuclear cells, were detected in albino rats of an early age. In parallel, the presence of lipofuscin was detected in the isolated vascular layer (choroid) of the retina that underlies RPE. The relationship between the early appearance of signs of aging in the RPE of albino rats and the absence of the melanin pigment in the cells of this tissue is discussed. The obtained data should be taken into account when conducting experimental ophthalmological studies on this animal model object.









Similar content being viewed by others
REFERENCES
Adams, T., Shahabi, G., Hoh-Kam, J., and Jeffery, G., Held under arrest: many mature albino rpe cells display polyploidal features consistent with abnormal cell cycle retention, Exp. Eye Res., 2010, vol. 90, no. 2, pp. 368–337.
Al-Hussaini, H., Vugler, A., Semo, M., and Jeffery, G., Mature mammalian retinal pigment epithelium cells proliferate in vivo, Mol. Vision, 2008, vol. 14, pp. 1784–1791.
Batista, T.M., Tomiyoshi, L.M., Dias, A.C., et al., Age-dependent changes in rat lacrimal gland anti-oxidant and vesicular related protein expression profiles, Mol. Vision, 2012, vol. 18, pp. 194–202.
Bodenstein, L. and Sideman, R., Growth and development of the mouse retinal pigment epithelium. Cell and tissue morphometrics and topography of mitotic activity, Dev. Biol., 1987, vol. 121, pp. 192–204.
Chen, M., Rajapakse, D., Fraczek, M., et al., Retinal pigment epithelial cell multinucleation in the aging eye—a mechanism to repair damage and maintain homoeostasis, Aging Cell, 2016, vol. 15, pp. 436–445.
Cortese, K., Giordano, F., Surace, E.M., et al., The ocular albinism type 1 (OA1) gene controls melanosome maturation and size, Invest. Ophthalmol. Vis. Sci., 2005, vol. 46, no. 12, pp. 4358–4364.
Grigoryan, E.N., Competence factors of retinal pigment epithelium cells for reprogramming in the neuronal direction during retinal regeneration in newts, Izv. Ross. Akad. Nauk, Ser. Biol., 2014, no. 1, pp. 5–16.
Grigoryan, E.N., Novikova, Y.P., and Gancharova, O.S., New antioxidant SkQ1 is an effective protector of rat eye retinal pigment epithelium and choroid under conditions of long-term organotypic cultivation, Adv. Aging Res., 2012, vol. 1, pp. 31–37.
Grønskov, K., Ek, J., and Brondum-Nielsen, K., Oculocutaneous albinism, Orphanet. J. Rare Dis., 2007, vol. 2, pp. 43–53.
Gu, X., Neric, N.J., Crabb, J.S., Crabb, J.W., et al., Age-related changes in the retinal pigment epithelium (RPE), PLoS One, 2012, vol. 7, no. 6, e38673.
Gutteridge, J.M.C., Fluorescent products of phospholipid peroxidation: formation and inhibition in model systems, in Ceroid Lipofuscinosis (Batten’s Sisease), Armstrong, D., Koppang, N., and Rider, J.A., Eds., Amsterdam: Elsevier Biomedical Press, 1982, pp. 351–364.
Ilia, M. and Jeffery, G., Retinal mitosis is regulated by DOPA, a melanin precursor that may influence the time at which cells exit the cell cycle: analysis of patterns of cell production in pigmented and albino retinae, J. Comp. Neurol., 1999, vol. 405, pp. 394–405.
Iwai, L., Ramos, A., Schaler, A., et al., Retinal pigment epithelial integrity is compromised in the developing albino mouse retina, J. Comp. Neurol., 2016, vol. 524, no. 18, pp. 3696–3716.
Katz, M.L., Incomplete proteolysis may contribute to lipofuscin accumulation in the retinal pigment epithelium, Adv. Exp. Med. Biol., 1989, vol. 266, pp. 109–116.
Kennedy, C.J., Rakoczy, P.E., and Constable, I.J., Lipofuscin of the retinal pigment epithelium: a review, Eye (London), 1995, vol. 9, pp. 763–771.
Mazzoni, F., Safa, H., and Finnemann, S.C., Understanding photoreceptor outer segment phagocytosis: use and utility of RPE cells in culture, Exp. Eye Res., 2014, vol. 126, pp. 51–60.
Nadal-Nicolás, F.M., Salinas-Navarro, M., Jiménez-López, M., et al., Displaced retinal ganglion cells in albino and pigmented rats, Front. Neuroanat., 2014, vol. 8, pp. 99–105.
Nag, T.C., Maurya, M., and Sankar, RoyT., Age-related changes of the human retinal vessels: possible involvement of lipid peroxidation, Ann. Anat., Anatomischer Anzeiger, 2019, vol. 226, pp. 35–47.
Novikova, Yu.P., Gancharova, O.S., Eichler, O.V., et al., Preventive and therapeutic effects of SkQ1 containing Visomitin eye drops against light induced retinal degeneration, Biochemistry (Moscow), 2014, vol. 79, pp. 1101–1110.
Rozanowska, M., Properties and functions of ocular melanins and melanosomes, in Melanins and Melanogenesis: Biosynthesis, Biogenesis, Physiological and Pathological Functions, Borovansky, J. and Riley P.A., Eds., Weinheim, Germany: Wiley-Blackwell, 2011, pp. 187–224.
Sarna, T., Properties and function of ocular melanin-a photophysical view, J. Photochem. Photobiol. Biol. B., 1992, vol. 12, pp. 215–258.
Smith, R.T., Farsiu, S., and Allingham, M., Understanding RPE lipofuscin, Invest. Ophthalmol. Vis. Sci., 2016, vol. 57, no. 15, pp. 6766–6772.
Sparrow, J.R., Hicks, D., and Hamel, C.P., The retinal pigment epithelium in health and disease, Curr. Mol. Med., 2010, vol. 10, no. 9, pp. 802–823.
Strauss, O., The retinal pigment epithelium in visual function, Physiol. Rev., 2005, vol. 85, no. 3, pp. 845–881.
Summers, C.G., Albinism: classification, clinical characteristics, and recent findings, Optom. Vis. Sci., 2009, vol. 86, pp. 659–662.
Sundelin, S.P., Nilsson, S.E.G., and Brunk, U.T., Lipofuscin formation in cultured retinal pigment epithelial cells is related to the melanin content, Free Radical Biol. Med., 2001, vol. 30, no. 1, pp. 74–81.
Wang, N., Koutz C.A., Anderson R.E., A method for the isolation of retinal pigment epithelial cells from adult rats, Invest. Ophthalmol. Vis. Sci., 1993, vol. 34, no. 1, pp. 101–107.
Young, R.W., The renewal of rod and cone outer segments in the rhesus monkey, J. Cell Biol., 1971, vol. 49, pp. 303–309.
ACKNOWLEDGMENTS
We thank O.V. Kilina (MSU) for her assistance at the initial stage of conducting experiments. The work was carried out using the equipment of the Core Centrum of Koltzov Institute of Developmental Biology, Russian Academy of Sciences.
Funding
The work was performed within the framework of State Assignment of Koltzov Institute of Developmental Biology of Russian Academy of Sciences, 2020, no. 0108-2020-0005).
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of interest. The authors declare that they have no conflict of interest.
Statement on the welfare of animals. During this study, all manipulations performed with experimental animals, methods of anesthesia, euthanasia, and animal care before and after experimental interventions matched international standards on bioethics.
AUTHOR CONTRIBUTIONS
Yu.P. Novikova participated in experiments and data processing, E.N. Grigoryan participated in conducting experiments, analyzing results, and writing articles.
Additional information
Translated by A. Ermakov
Rights and permissions
About this article
Cite this article
Novikova, Y.P., Grigoryan, E.N. Early Appearance of Aging Signs in the Retinal Pigment Epithelium in Young Albino Rats. Russ J Dev Biol 51, 377–386 (2020). https://doi.org/10.1134/S1062360420060065
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S1062360420060065

