Do Stem Cells Migrate to the Retina?

Abstract

Cell technologies are one of the modern methods of therapy in retina diseases. Stem cells (SC) are injected into systemic circulation or intravitreally, which is sometimes accompanied by side effects or ineffective. Many pathological processes in retina (retinopathy, macular degeneration, retinal angiopathy and others) require the use of really effective reparative technologies. Considering the ability of mesenchymal SCs (MSCs) to migrate during perineural implantation to damaged areas of nervous tissue, experiments were carried out on Wistar rats (n=10). One eye was enucleated and simultaneous parabulbar injection of 100000 MSCs labeled with CD90 + PKH67 in 100 μl of buffer solution into the intact eye was performed under ketamine-xylazine-acepromazine (55.6, 5.5 and 1.1 mg/kg, respectively) anesthesia. Enucleation model is accompanied by damage to cranial nerves and development of neurodestructive phenomena in the brain. Horizontal sections of brain (8 microns) and retina (12 microns) were made in three days after decapitation of animals. Preparations were examined using a Zeiss Axio Vert 200M fluorescence microscope. The next hypothesis was verified during the process: damage to II, III, IV and VI cranial nerves during enucleation, including centrifugal fibers from the nuclei of brain to retinal neurons [Reperant J, et al. 2006, 2007], is accompanied by neurodestructive phenomena not only in brain structures (quadrigemina of mesencephalon, lateral geniculate body of diencephalon, visual cortex), but in the retina also. Fluorescent MSCs were visualized in the above regions of brain and in all layers of retina. It has been suggested that neurodestructive phenomena develop in subcortical nuclei of brain after unilateral enucleation and damage to centripetal and centrifugal nerve fibers. These processes trigger migration of implanted MSCs to the damaged areas of brain and their subsequent return migration along centripetal and centrifugal nerve fibers to the damaged retina of “intact” eye. Disturbed innervation due to damaged nerve fibers after enucleation leads to destructive processes in this eyeball and triggers migration of MSCs into the retina of an “intact” eye from brain. Thus, methodological possibilities of MSCs delivery to damaged areas of the retina by means of implantation of MSCs into the region of cranial nerves of eyeball have been demonstrated. Additional implantation of MSCs, not only para- and retrobulbar, but also along with intranasal implantation of MSCs in the area of olfactory and trigeminal nerve terminals is quite realistic. The use of MSCs’ ability to migrate into damaged biological tissues (including areas of neurodestruction in the brain and retina) is an applied aspect of such implantations in clinical practice. It is known that reparative ability of MSCs in damaged areas of brain and retina is manifested after release of various neurotrophic factors in the foci of neurodestruction.