[Experimental stem cell replacement transplantation in retinal pigment epithelium atrophy]. / Zamestitel'naya transplantatsiya stvolovymi kletkami pri atrofii retinal'nogo pigmentnogo epiteliya v eksperimente.

PURPOSE: To develop and evaluate the results of the modified surgical technique for transplantation of retinal pigment epithelium (RPE) differentiated from human induced pluripotent stem cells (iPSC-RPE) in the form of a cell suspension into the subretinal space of rabbits with previously induced RPE atrophy. MATERIAL AND METHODS: The study was conducted on 10 New Zealand albino rabbits (20 eyes). One month after modeling RPE atrophy and retinal degeneration, rabbits were subjected to subretinal transplantation of iPSC-RPE cells in the form of a cell suspension. To prevent reflux of iPSC-RPE into the vitreal cavity, the injection site was sealed with 2-3 drops of autologous platelet-rich plasma (PRP). All rabbits underwent spectral optical coherence tomography (SOCT) and autofluorescence studies on the Heidelberg Spectralis system («Heidelberg Engineering¼, Germany). Enucleated animal eyes were studied with morphological and immunohistochemical methods. RESULTS: In this study we developed and evaluated a modified surgical technique of transplantation of iPSC-RPE in the form of a cell suspension into the subretinal space of rabbits with induced RPE atrophy. It was found that the use of PRP helps seal the defect and prevents cell suspension reflux into the vitreous cavity, effectively minimizing intra- and postoperative complications. Morphological in vivo study and examination of histological sections showed that implantable iPSC-RPEs were correctly integrated and adhered to the choroid in the surgery site. Immunohistochemical analysis involving fluorescence-marked antibodies confirmed the survival of iPSC-RPE integrated into the retina of model animals. CONCLUSION: This method improves the technology of iPSC-RPE transplantation on preclinical stages of the study, revealing new prospects in the treatment of degenerative diseases of the retina and the possibility of a personalized approach.

[Electroretinographic signs of retinal remodeling after experimental induction of retinal pigment epithelium atrophy]. / Elektroretinograficheskie priznaki remodelirovaniya setchatki posle induktsii atrofii retinal'nogo pigmentnogo epiteliya v eksperimente.

Various animal models of atrophy of retinal pigment epithelium (RPE) are created in order to study certain aspects of geographical atrophy in humans. To study the effects of new methods of therapy, it is necessary to determine the objective functional markers of structural changes in the retina. PURPOSE: To determine the alterations in activity of the retina that characterize its remodeling in induction of RPE atrophy. MATERIAL AND METHODS: Full-field electroretinograms (ERG), pattern ERG, and multifocal ERG were recorded according to the ISCEV standards from the right eyes of twenty rabbits of the New Zealand albino breed 6-7 weeks after induction of RPE atrophy by subretinal administration of 0.9% sodium chloride or bevacizumab solution. RESULTS: Characteristic electroretinographic signs of RPE atrophy and retinal remodeling are described. Changes in ERG indicate a predominant inhibition of the functional activity of photoreceptors compared with bipolar cells, which objectively reflects an impairment of their metabolism associated with RPE pathology. With the injection of bevacizumab, a sharp weakening of the functional symbiosis of Mueller cells with bipolar cells was observed. According to pattern ERG, the function of the retinal ganglion cells was reduced. The reaction of the paired eyes after induction of RPE atrophy included a moderate decrease in the amplitude of b-wave of photopic ERG and activation of glia-neuronal relationships. CONCLUSION: Subretinal injections of 0.9% sodium chloride and bevacizumab trigger changes in the retina that reflect specific remodeling of retinal neurons of the second and third orders, which characterizes the used models of RPE atrophy.