RU2428956C2 - Method of treating optic nerve by transplantation of autologic stem cells - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: method includes delivery of biological material into area of optic nerve by injection parabulbarly, as well as by means of two microdrainages through the incision of sclera into sub-Tenon's and suprachoroidal spaces of eye. As biological material used is autologic cell material in form of suspension of bone marrow mononuclears, which contains patient's stem cells on carrier solution in concentration from 100000 to 1000000 cells per ml of suspension. Introduction is performed in portions every 1-2 hours up to 10 times per day for each separate way of introduction. Parabulbarly 1 ml per injection is introduced. Through microdrainages in sub-Tenon's space introduced are 1-4 ml per injection, into suprachoroidal space - 0.1-0.3 ml per injection.

EFFECT: reduction of blindness and visual impairedness with restoration of structure and functioning of optic nerve due to induction of organotypic tissue regeneration, including vascular net of optic nerve, its disc and peripapillar choroidea.

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Description

The invention relates to medicine, namely to ophthalmology, and can be used to treat visual atrophy. Atrophy of the optic nerve is one of the main causes of low vision and blindness.

The objective is to reduce blindness and low vision with optic atrophy. The optic nerve may be damaged due to: 1) injury; 2) tumors; 3) inflammatory diseases; 4) high intraocular pressure in glaucoma; 5) vascular changes in atherosclerosis and hypertension; 6) poisoning with alcohol substitutes (low-quality alcohol); 7) poisoning with other chemicals that have a detrimental effect on the optic nerve tissue; 8) occlusion of the vessels of the eye with a thrombus or embolus. Whatever the cause of the atrophy of the optic nerve, the essence of the disease is that the blood flow in the smallest capillaries that feed the membranes and fibers of the optic nerve is disrupted. As a result, the destruction of nerve fibers occurs, their replacement with glial and connective tissue, the ability of the nerve to transmit signals - visual impulses to the brain, suffers. The optic nerve is powered by a huge number of small vessels of four arterial systems: retinal, choroidal, scleral and meningeal. But mainly with the posterior short ciliary arteries, the central retinal artery extending from the trunk of the ophthalmic artery, and the plexus branches of the pia mater, which limits the possibilities of the microsurgical method of revascularization of the optic nerve.

In case of optic atrophy, surgical methods are used, including vasoreconstructive surgery, subtenon space catheterization with the introduction of drugs into this area, implantation of electrodes to the optic nerve disk, and transplantation of various biomaterials (parts of the oculomotor muscles, own adipose tissue, preserved donor cadaveric material - alloplant).

There is a method of treating optic atrophy with Alloplant biomaterial, which can stimulate the regeneration of capillaries. An alloplant is a plate of donated canned tissue with a deep notch for the optic nerve at one end (Alloplant for revascularization of the optic nerve). The alloplant plate is inserted into the suprachoroidal space of the eye, carefully guided to the posterior pole of the eye, where the optic nerve enters the eye capsule, and “sits” the notch onto the optic nerve, and the two “legs” are straightened along the edges of the notch so that Alloplant has good contact with the visual the nerve. This biomaterial stimulates neoangiogenesis, through which blood vessels grow from the surface of the sclera into the optic nerve and normalize its capillary circulation, eliminating optic atrophy (Karushin O.I. Surgical treatment of optic atrophy in primary glaucoma using alloplant biomaterial, abstract of diss. Candidate of Medical Sciences, Krasnoyarsk, 1998, S. 19. RU 2071302 C1, 10.01.1997, RU 2141809 C1, 11.27.1999. RU 2049452 C1, 12.10.1995; Muldashev ER, Muslimov SA, Nigmatullin R.T., Kiiko YI, Galimova VU, Salikhov AY, Selsky NE, Bulatov R.T., Musina LA Basic research conducted on Alloplant biomaterials. European Journal of Ophthalmology. - 1999.- Vol. .9, No. 1. - P.8-13).

The disadvantages of this method are: the invasiveness of the operation, the risk of adverse reactions to allogeneic material. The effect of revascularization is mediated through the provocation of an aseptic inflammatory reaction, which carries the risk of progression and transition to chronic inflammation, possibly with the addition of an autoimmune component. Immunoprivilege of the eye, the ophthalmic hematological barrier may be impaired. There are risks of excessive scarring, destroying the retina, or scarring of the optic nerve.

The technical result of the invention is the reduction of blindness and low vision during optic atrophy during restoration of the structure and function of the optic nerve due to the induction of organotypic tissue regeneration, including the vasculature of the optic nerve, its disk and peripapillary choroid with autologous bone marrow stem cells.

The technical result is achieved by the fact that autologous bone marrow mononuclear cells containing several stem cell populations, including proangiogenic, endothelial progenitor, hematopoietic and mesenchymal, are injected parabulbularly and suspension fractionally into subtenon via a suspension on a carrier solution (Nesterov A. P., Basinsky S.N. A new method of administering drugs to the posterior section of the subthenon space. // Bulletin of Ophthalmology, 1991, N 5, p. 49-51) and suprachoroid space wa (T.W.Olsen Treatment of exudative age-related macular degeneration:. many factors to consider Ocular Surgery News 2007. - Vol.25.- No 2. - P.14) the patient's eye.

The method is carried out in two stages.

First step. In a patient from the iliac wing under local anesthesia, outpatient sampling of bone marrow in an amount of 10-60 ml is performed aseptically. A bone marrow aspirate with an anticoagulant is transmitted to the cell technology laboratory. In the laboratory, under aseptic conditions, bone marrow material is prepared from the bone marrow in the form of a suspension of mononuclear cells in an isotonic aqueous solution. As cell material, not only autologous mononuclear cells can be used, but also cultivated multipotent mesenchymal stromal cells of bone marrow and adipose tissue. Some of the cells are frozen in liquid nitrogen and transferred to a cryobank, for possible subsequent use.

Second phase. After 1-1.5 hours after bone marrow collection, autologous mononuclear cells isolated from it in the form of a suspension on a carrier solution are injected parabulbularly and, after two pre-installed microdrainages, are divided into subtenon (1-4 ml per injection) and suprachoroidal (by 0.1-0.3 ml per injection) of the patient’s eye space. The operation takes a minimum of time and is less traumatic. Microdrainages are left for a day. After 1-2 hours, the mononuclear cells are reintroduced in an amount from 100,000 to 1,000,000 cells per ml, no more than 10 times per day.

Depending on the results of treatment, in 1-2 months it is possible to conduct repeated similar cell transplantations in order to improve and consolidate the results of treatment.

With this method of transplantation, bone marrow stem cells exhibit well-known properties, namely: they activate neoangiogenesis, increasing blood circulation in the vessels of the retina and optic nerve of the eye, and improve trophism of nerve cells and their processes. Conditions are created that stimulate organotypic tissue regeneration, in this case, the intraorbital part of the visual analyzer. That allows you to effectively restore impaired visual function.

Organotypic regeneration of ocular nerve tissue in this method of treating optic atrophy can be associated not only with the plastic function of stem cells - a source of tissue regeneration - with subsequent differentiation and transformation into the desired population of specialized cells, but also with the well-known, so-called trophic effect: stem cells produce bioactive factors that inhibit apoptosis suppress tissue fibrosis, scar formation, have angiogenic properties, i.e. initiate the growth of new capillaries, enhance the division of local stem cells. An important ability of transplanted stem cells is the suppression of the autoimmune process in a pathologically altered organ of vision, which, given its immunopreference, is extremely important for the full restoration of visual function.

Clinical examples.

Example 1

Patient R., 68 years old.

OD - open angle glaucoma IIa

OS - open-angle glaucoma IIIc.

Visual acuity: OD = 0.4s-1.0d = 0.5

OS = 0.02c + 10.0d = 0.1

OS - calm, turned to the outside by 15-20 degrees.

Aphakia. The remains of the posterior capsule along the edge of the pupil.

The pupil is tightened at 12.30 o’clock. The optic disc is white, glaucomatous excavation.

IOP = OD = 20 mmHg

OS = 26 mmHg

13 days after the introduction of autologous stem cells:

Visual acuity - OD = s-1.0d = 0.7

OS = s + 10.0d = 0.4.

IOP = OD = 19 mmHg

OS = 23 mmHg

According to the patient, the field of vision expanded from the temporal side, vision improved.

Objectively: Ph.D. pink on the bow, a pink rim is visible along the edge of the disc.

In 1 month. Vision: OD = s-1.0 = 0.7

OS = s10.0 = 0.6

IOP = OD = 19 mmHg

OS = 21 mmHg

The dynamics are positive. Process stabilization. Repeated administration of autologous stem cells parabulbarno.

3 months after the first injection:

Visual acuity - OD = s-1.0d = 0.7

OS = s + 10.0d = 0.6.

IOP = OD = 19 mmHg

OS = 21 mmHg

OS is calm. Deviated outward by 10 degrees.

Aphakia, Pink optic nerve disc, slight temporal decolorization. Selected contact lens on OS + 9.0d.

Example 2

Patient K., 58 years old.

From the anamnesis: 54 years ago, a benign brain tumor in the area of chiasma was removed. After the operation, the patient lost his sight.

Vision of both eyes; = 0.01 n / k. The anterior segment of the eye is normal.

Fundus: Disks of optic nerves of white color.

Diagnosis: Downward atrophy of the optic nerves in both eyes.

Parabulbar and suprachoroidal administration of autologous stem cells was performed.

After 1 month - vision of both eyes = 0.05 n / a

IOP is the norm. Optic nerve disc with a slight pink tint.

Autologous stem cells were reintroduced.

Thus, these clinical examples clearly illustrate the high efficiency of the proposed method of treatment. This method is easy to use and can be performed in a wide network of ophthalmic clinics.

Claims (1)

A method of treating optic atrophy, including the delivery of biological material to the optic nerve region, characterized in that the delivery is carried out by injection parabulbarly, as well as using two microdrainages through the through sclera incision into the subtenon and suprachoroidal spaces of the eye, and autologous cellular material is used as biological material in the form of a suspension of bone marrow mononuclear cells containing patient stem cells on a carrier solution in a concentration of from 100,000 to 1,000,000 cells to in ml of suspension, the introduction is carried out fractionally every 1-2 hours up to 10 times a day for each individual route of administration, while 1 ml is injected parabulbarly, through microdrainages, 1-4 ml per injection is injected into the subtenon space, into the suprachoroid space - 0.1-0.3 ml per injection.