Alterations of STEP46 and STEP61 Expression in the Rat Retina with Age and AMD-Like Retinopathy Development

Alterations of STEP46 and STEP61 Expression in the Rat Retina with Age and AMD-Like Retinopathy Development Full article

Journal

International Journal of Molecular Sciences
ISSN: 1661-6596

Output data

Year: 2020, Volume: 21, Number: 15, Article number : 5182, Pages count : DOI: 10.3390/ijms21155182

Tags

age-related macular degeneration; striatal-enriched protein tyrosine phosphatase; Ptpn5; STEP46; STEP61; TC-2153; OXYS rats

Authors

Telegina Darya, V ¹ , Kulikova Elizabeth A. ¹ , Kozhevnikova Oyuna S. ¹ , Kulikov Alexander, V ¹ , Khomenko Tatyana M. ² , Volcho Konstantin P. ² , Salakhutdinov Nariman F. ² , Kolosova Nataliya G. ^1,2

Affiliations

1	(Данные Web of science) Russian Acad Sci SB RAS, Siberian Branch, Inst Cytol & Genet, Pr Lavrentyeva 10, Novosibirsk 630090, Russia
2	(Данные Web of science) SB RAS, NN Vorozhtsov Inst Organ Chem, 9 Lavrentieva Ave, Novosibirsk 630090, Russia

Tyrosine phosphatase STEP (striatal-enriched tyrosine protein phosphatase) is a brain-specific protein phosphatase and is involved in the pathogenesis of many neurodegenerative diseases. Here, we examined the impact of STEP on the development of age-related macular degeneration (AMD)-like pathology in senescence-accelerated OXYS rats. Using OXYS and Wistar rats (control), we for the first time demonstrated age-dependent changes inPtpn5mRNA expression, STEP46 and STEP61 protein levels, and their phosphatase activity in the retina. The increases in STEP protein levels and the decrease of total and STEP phosphatase activities in the retina (as compared with Wistar rats) preceded the manifestation of clinical signs of AMD in OXYS rats (age 20 days). There were no differences in these retinal parameters between 13-month-old Wistar rats and OXYS rats with pronounced signs of AMD. Inhibition of STEP with TC-2153 during progressive AMD-like retinopathy (from 9 to 13 months of age) reduced the thickness of the retinal inner nuclear layer, as evidenced by a decreased amount of parvalbumin-positive amacrine neurons. Prolonged treatment with TC-2153 had no effect onPtpn5mRNA expression, STEP46 and STEP61 protein levels, and their phosphatase activity in the OXYS retina. Thus, TC-2153 may negatively affect the retina through mechanisms unrelated to STEP.

Telegina D.V. , Kulikova E.A. , Kozhevnikova O.S. , Kulikov A.V. , Khomenko T.M. , Volcho K.P. , Salakhutdinov N.F. , Kolosova N.G.
Alterations of STEP46 and STEP61 Expression in the Rat Retina with Age and AMD-Like Retinopathy Development

International Journal of Molecular Sciences. 2020. V.21. N15. 5182 . DOI: 10.3390/ijms21155182 WOS Scopus

Full text from publisher

Published online:

Jul 22, 2020

Web of science	WOS:000559519200001
Scopus	2-s2.0-85088297484
OpenAlex	W3045090917