Retinal diseases accompanied with the dysfunction or death of the retinal pigment epithelial (RPE) cells are widespread, hard to treat, and appear to be a leading case of visual loss and blindness among the persons older than 55 years. Transplantation of RPE cells derived from the induced pluripotent stem cells (IPSC-RPE) is a promising method of therapy for these diseases. To ensure the transplant survival instant follow-up is required. It can be based on biochemical analyses of tear fluid that can be easily non-invasively collected. For the post-transplantation process monitoring we have choosen such polyfunctional bioregulators as α2-macroglobulin (α2-MG) and endothelin-1 (ET-1). RPE atrophy in New Zealand Albino rabbits was modeled via the subretinal injection of bevacizumab. IPSC-RPE in suspension or as a monolayer on the scaffold were transplanted subretinally 1 month after the injection. α2-MG activity and ET-1 concentration in tears were estimated during the first month and after 2, 3 and 7 months after transplantation. On the 7-14 days after transplantation α2-MG activity increased in tears of the both operated and controlateral eye probably as a reaction on the corticosteroid therapy. In 50% rabbits there was one more increase after 2-3 months that could be due to the immune inflammation. Concentration of ET-1 in tears decreased dramatically on the 7-14 days and 7 months after transplantation, and it could have an influence upon the retinal vassal tone. The data obtained show that estimation of bioregulators in tears can help monitoring local metabolic processes after RPE transplantation that is necessary for the opportune, reasonable and focused medicamental correction of post-transplantation process.
Zabolevaniia setchatki, sviazannye s narusheniem funktsionirovaniia ili gibel'iu kletok retinal'nogo pigmentnogo épiteliia (RPÉ), shiroko rasprostraneny, trudno poddaiutsia lecheniiu i vo vsem mire iavliaiutsia vedushcheĭ prichinoĭ slepoty i slabovideniia. Transplantatsiia kletok RPÉ, differentsirovannykh iz indutsirovannykh pliuripotentnykh stvolovykh kletok (IPSK-RPÉ), iavliaetsia perspektivnym metodom lecheniia étikh zabolevaniĭ. Dlia obespecheniia dolgosrochnoĭ vyzhivaemosti transplantata neobkhodimo dinamicheskoe nabliudenie za posttransplantatsionnym protsessom. Materialom dlia otsenki metabolicheskikh izmeneniĭ v setchatke mozhet sluzhit' sleznaia zhidkost', dostupnaia dlia neinvazivnogo polucheniia i issledovaniia v dinamike protsessa. S tsel'iu poiska biomarkerov v sleznoĭ zhidkosti, otrazhaiushchikh kharakter techeniia posttransplantatsionnogo protsessa v setchatke, byli vybrany polifunktsional'nye bioreguliatory — α2-makroglobulin (α2-MG) i éndotelin-1 (ÉT-1). U krolikov modelirovali atrofiiu RPÉ putem subretinal'nogo vvedeniia rastvora bevatsizumaba i cherez mesiats v subretinal'noe prostranstvo vvodili IPSK-RPÉ v vide suspenzii ili v vide monosloia na biosovmestimoĭ membrane, imitiruiushcheĭ nativnuiu membranu Brukha. Aktivnost' α2-MG v sleznoĭ zheleze povyshalas' v opytnom i parnom glazakh na 7-14 den' posle transplantatsii za schet deĭstviia primeniaemoĭ v étot period kortikosteroidnoĭ terapii i u 50% krolikov cherez 2-3 mesiatsa, po-vidimomu, vsledstvie razvitiia vospalitel'noĭ immunnoĭ reaktsii. Soderzhanie ÉT-1 v sleznoĭ zheleze rezko padalo na 7-14 den' i cherez 7 mesiatsev posle transplantatsii, chto mozhet vliiat' na tonus sosudov v tkaniakh glaza. Poluchennye rezul'taty svidetel'stvuiut, chto issledovanie bioreguliatorov v sleznoĭ zhidkosti mozhet pozvolit' provodit' monitoring lokal'nykh metabolicheskikh protsessov posle peresadki RPÉ, chto vazhno dlia provedeniia svoevremennoĭ, obosnovannoĭ i personalizirovannoĭ medikamentoznoĭ korrektsii posttransplantatsionnogo protsessa.
Keywords: endothelin-1; induced pluripotent stem cells; optical coherent tomography; retinal pigment epithelium; tears; transplantation.