MXPA99007449A - Method for destroying retinal pigment epithelial cells - Google Patents
Method for destroying retinal pigment epithelial cellsInfo
- Publication number
- MXPA99007449A MXPA99007449A MXPA/A/1999/007449A MX9907449A MXPA99007449A MX PA99007449 A MXPA99007449 A MX PA99007449A MX 9907449 A MX9907449 A MX 9907449A MX PA99007449 A MXPA99007449 A MX PA99007449A
- Authority
- MX
- Mexico
- Prior art keywords
- basement membrane
- vitreous chamber
- binding agent
- membrane binding
- destroying
- Prior art date
Links
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Abstract
A method for destroying retinal pigment epithelial cells in an eye in order to prevent the occurence of proliferative vitreoretinopathy. A solution containing a basement membrane binding agent conjugated to a cytotoxic agent is introduced into the vitreous chamber. The solution is maintained in the vitreous chamber for a period of time sufficient to permit the basement membrane binding agent to bind to basement membranes lining the vitreous chamber. The solution is then removed from the vitreous chamber, whereby a portion of the basement membrane binding agent remains bonded to basement membranes within the vitreous chamber, thereby exposing retinal pigment epithelial cells disposed on the basement membrane to the cytotoxic agent.
Description
METHOD FOR DESTROYING EPITHELIAL CELLS
WITH RETINAL PIGMENT
FIELD OF THE INVENTION
The present invention relates to a method for destroying the pigment and proliferative epithelial cells of this type of the retina, in order to avoid the appearance of proliferative vitreoretinopathy (VRP) or the formation of traction bands following the current treatment. for tears and retinal detachments. More specifically, the present invention is directed to a method for destroying retinal pigment and proliferative epithelial cells of this type on the surface of the retina in the vitreous chamber of the eye through the application of a membrane binding agent having a toxin attached to it.
PREVIOUS TECHNIQUE
Proliferative vitreoretinopathy (VRP) is the most common cause of blindness after retinal detachment. In order to gain access to a torn or detached retina, an incision is typically made in the pars plana of the eye in order to introduce a surgical instrument into the vitreous chamber of the eye. In the case of retinal tears and detachments, a vitrectomy and reattachment procedure is performed, in which a torn or detached portion of the retina is reattached using a surgical laser instrument, cautery, adhesives or tampons. After detachment or retinal tears, proliferating cells are released, such as, but not limited to, pigment epithelial cells of the retina, glial cells, fibroblasts, macrophages, myofibroblast cells, and others similar to the vitreous camera. These proliferative cells, which are thought to be primarily retinal pigment epithelial cells (EPR) and which are therefore collectively referred to as EPR cells, then proliferate in the vitreous chamber. The pro-life of these cells in the vitreous chamber and in the retina produces traction bands to form and detach the retina again, thus causing blindness. Accordingly, a method of prevention of pro-life vitreoretinopathy is desired. Likewise, a composition that is useful in the prevention of proliferative vitreoretinopathy is desired.
DESCRIPTION OF THE INVENTION
The method of the present invention is used to destroy retinal pigment epithelial cells in the vitreous chamber of the eye after a tear or a retinal detachment, through the use of a basement membrane binding agent. Preferably, a cytotoxic agent capable of destroying pigment epithelial cells of the retina is conjugated to the basement membrane binding agent. After the vitrectomy, if necessary, and to reattach the retina, the basement membrane binding agent conjugated to the cytotoxic agent is introduced into the vitreous cavity of the eye. The basement membrane binding agent conjugated to the cytotoxic agent is allowed to remain in the vitreous chamber for a predetermined period of time sufficient to allow the basement membrane binding agent to bind to the basement membrane lining the vitreous chamber of the membrane. eye and, more specifically, to the internal limiting membrane (MLI). Any excess material is then removed from the vitreous chamber. It is then exposed to the retinal pigment epithelial cells released to the vitreous chamber and subsequently placed on the basement membranes to the cytotoxic agent conjugated to the basement membrane binding agent, resulting in the destruction of retinal pigment epithelial cells. In an alternative embodiment of the method of the present invention, preferably for use in pyschotic eyes, a first basement membrane binding agent is introduced into the eye prior to performing a vitrectomy. The first basement membrane binding agent is allowed to remain in the eye for a predetermined period of time sufficient to allow the basement membrane binding agent to bind to the basal membranes in the eye. The excess of the first basal membrane binding agent of the eye is then removed. A vitrectomy is then performed, if necessary, and the retina is reattached, thus exposing the additional basal membranes within the vitreous chamber. A second basement membrane binding agent having a cytotoxic agent conjugated thereto is then introduced into the eye and allowed to remain there for a sufficient period of time to allow the basement membrane binding agent to bind to the membranes. basics inside the vitreous camera. Any excess material is removed from the eye. The retinal pigment epithelial cells arranged on the basal membranes in the vitreous chamber are, therefore, exposed to the cytotoxic agent conjugated to the second basement membrane binding agent, resulting in the destruction of retinal pigment epithelial cells.
MODE (S) OF CARRYING OUT THE INVENTION
The method of the present invention aims to destroy the proliferative cells, collectively referred to collectively as retinal pigment epithelial cells, disposed on the inner surfaces of the vitreous chamber of the eye. By destroying these cells, the cells can not proliferate and / or migrate along the surface of the retina and form traction bands, which are indicative of proliferative vitreoretinopathy (VRP), leading to retinal detachment. The method in question is, therefore, capable of preventing the appearance of proliferative vitreorhythmopathy (VRP). The method of the present invention can be employed in relation to any retinal gathering procedure. Vitrectomy and retinal assembly involves the formation of an incision through the surface of the eye in order to achieve direct access to the inner vitreous chamber of the eye. Although the necessary incision is normally formed in the pars plana of the eye, it will be appreciated that alternative locations for this incision can be selected at the discretion of the surgeon. After the formation of the incision, a vitrectomy is usually required and is performed before introducing a cautery instrument through the incision into the vitreous chamber of the eye. The instrument, usually a laser, advances through the vitreous chamber, such that the laser, or a similar suitable instrument is in direct contact with the surface of the retina of the eye. The retina is united again through the use of the laser for its cauterization. Alternatively, the retina can be reattached using suitable adhesives and / or buffers. It has been discovered that certain agents bind to the basal membranes, including the basal membranes inside the vitreous chamber. Basal membrane binding agents, when bound to the basement membrane or to the MLI of the vitreous chamber, are in direct contact with the retina pigment epithelial cells during the progression of the VRP. The method of the present invention is based on observations of said cell proliferation. In a first embodiment of the method of the present invention, a solution containing a basement membrane binding agent is introduced into the vitreous chamber after a vyectomy, if performed, and the retinal assembly. In this first embodiment of the present invention, a cytotoxic agent is conjugated to the basement membrane binding agent. As indicated above, the basal mem-brane binding agent will bind to the basal membranes that form the inner surface of the vitreous chamber, thus providing direct contact between the retinal pigment epithelial cells and the cytotoxic agent conjugated to the vitreous agent. Basement membrane binding. The solution containing the basement membrane binding agent conjugated to the cyto-toxic agent is retained in the vitreous chamber for a predetermined period of time, sufficient to allow the basement membrane binding agent to bind to the basal membranes in the chamber vitrea. It will be appreciated that the amount of time required to attach the basement membrane binding agent to the basement membranes inside the vitreous chamber will depend on a number of factors, including, without limitation, the concentration of the basement membrane binding agent in the basement membrane. solution that is introduced into the vitreous chamber. The excess of the solution containing the basement membrane binding agent conjugated to the cytotoxic agent of the vitreous chamber is then removed. A variety of techniques can be used to eliminate this solution, including known suction and irrigation / aspiration techniques. After removal of the excess solution containing the basement membrane binding agent from the vitreous chamber of the eye, a buffer may or may not be applied and the incision in the eye is then closed to complete the procedure.
It will be appreciated that the basement membrane binding agent will remain attached to the basal membranes inside the vitreous chamber. The cytotoxic agent conjugated to the basement membrane binding agent will have, therefore, direct access to retinal pigment epithelial cells on the inner surface of the vitreous chamber. Specifically, it will be appreciated that the retinal pigment epithelial cells will come into contact with the basement membrane binding agent as the retinal pigment epithelial cells try to proliferate and migrate through the inner surface of the vitreous chamber. The retinal pigment epithelial cells will internalize the cytotoxic agent, thus leading to the destruction of the retinal pigment epithelial cells on the inner surface of the vitreous chamber and thus avoiding the VRP and the resulting blindness. In an aphakic eye, it should be noted that the anterior chamber of the eye is exposed to the vitreous chamber of the eye and also includes basal membranes, for example the corneal en-dotelum. Due to the fact that the corneal endothelium will not regenerate once it has been damaged, special care should be taken to ensure that the solution containing the basement membrane binding agent conjugated to a cytotoxic agent does not come into contact with the endothelium. -leal corneal. A second embodiment of the present invention aims to protect the corneal endothelium from the effects of the cytotoxic agent. In the second embodiment of the method of the present invention, a first solution containing a basement membrane binding agent without cytotoxic agent attached to it in the eye is introduced before performing a vitrectomy and retinal assembly. The ba-salt membrane binding agent in the first solution will bind to the exposed basal membranes within the eye, particularly to the corneal endothelium. The first solution containing a basement membrane binding agent is allowed to remain in the eye for a predetermined period of time sufficient to ensure that an adequate bond has been produced between the first basement membrane binding agent and the membranes. Basics inside the eye. The first solution containing a basement membrane binding agent is then removed from or or using known methods of aspiration or irrigation / aspiration, as indicated above with respect to the first embodiment of the present invention. A vitrectomy is then practiced, if necessary, and a retinal gathering procedure using known techniques. A second solution is then introduced containing a basement membrane binding agent conjugated to a cytotoxic agent in the vitreous chamber. It is preferable that the second solution binds only to those basal membranes within the eye not previously bound to the first basement membrane binding agent, thus ensuring that the cytotoxic agent destroys the reticular pigment epithelial cells in the vitreous chamber without damaging the corneal endothelium . For this reason, it is preferable that the first basement membrane binding agent be the same substance as the second basement membrane binding agent, thus ensuring that the first and second basement membrane binding agents bind to them. sites on the basement membranes. Polylysma can be used as a base membrane-binding agent in relation to the method of the present invention. It will be appreciated that the molecular weight of polylysine or other polymeric base-membrane binding agents may vary. This aspect of polymeric base-membrane binding agents makes them particularly beneficial in relation to the method of the present invention. Specifically, it will be appreciated that the binding affinity of a polymeric base-membrane binding agent, such as polylysine, will increase as its molecular weight increases, due to the greater number of binding sites available on the higher molecular weight molecule. Higher molecular weight polylysine molecules will thus tend to displace lower molecular weight polylysine molecules previously bound to a basement membrane. For the reasons indicated above, if a polymeric basement membrane binding agent, such as polylysine, is used in connection with the method of the present invention, it is preferable that the molecular weight of the first basement membrane binding agent be at least as high as the molecular weight of the second basement membrane binding agent, in order to ensure that the second basement membrane binding agent does not displace the first basement membrane binding agent. To further ensure that the second basal membrane binding agent does not displace the first basal membrane-binding agent, it is preferable that the molecular weight of the first base-membrane-binding agent be greater than the molecular weight of the second agent. of basement membrane binding. The second solution containing a basement membrane binding agent conjugated to a cytotoxic agent is retained in the vitreous chamber for a predetermined period of time sufficient to ensure that an adequate bond has been produced between the second basement membrane binding agent and the Basal membranes not previously bound to the first basement membrane binding agent. As indicated above, the amount of time required depends on a number of factors. The excess of the second eye solution is then removed using known techniques, such as aspiration or irrigation / aspiration. For the reasons discussed above with respect to the first embodiment of the present invention, the cytotoxic agent will tend to destroy the retinal pigment epithelial cells within the vitreous chamber, thereby preventing VRP. In a third embodiment of the present invention, the above-described steps of the first embodiment of the invention are carried out. Next, a second solution containing a second basement membrane binding agent is introduced and introduced into the eye in order to displace any first basement membrane binding agent that may have come into contact with the corneal endothelium. For the reasons discussed above, it is preferable that the second basement membrane binding agent be the same substance as the first base membrane binding agent. Furthermore, it is preferable that the molecular weight of the second basement membrane binding agent be greater than the molecular weight of the first basement membrane binding agent, thus ensuring that the second basement membrane binding agent displaces the first membrane binding agent. basal on the corneal endothelium. A variety of basal membrane binding agents can be used in connection with the method of the present invention. In a preferred embodiment of the present invention, polylysine is used as the basement membrane binding agent. It has been found that poly-L-lysine is effective when used in connection with the method of the present invention. It is possible that poly-D-lysine may also be effective. Polylysine is advantageously used in connection with the present invention, due to its availability, its relatively low cost and its ability to be formulated in a variety of molecular weights. Other basal membrane binding agents that are thought to be useful in connection with the present invention include, but are not limited to, fibronectin, fibroblast growth factors, laminin, type IV collagen, perlecan, deco-rine, thrombospondin, tenascin. , vitronectin, heparin, heparin sulfate, polyarginine, dextran, dextran sulfate, chondroitin sulfate, hyaluronic acid, platelet factor IV, fibrin and fibrinogen. A variety of cytotoxic agents can be used in conjunction with the method of the present invention. In a preferred embodiment of the present invention, a ribosomal inhibitory protein, such as saporin or ricin, is used as a cytotoxic agent. Ribosomal inhibitory proteins are preferable due to the fact that they contain more inhibitory activity per microgram than other cytotoxic agents that can be used in connection with the method of the present invention. Other cytotoxic agents that are believed to be effective when used in connection with the method of the present invention include, although without limitation, antimitotic drugs, such as methotrexate, 5-fluorouracil, daunomycin, doxorubicin, mitoxantrone, vinca alkaloids, vinblastine, colchicine or cytochains, when used as a cytotoxic agent. In addition, ionophores, such as monensin and ouabain, can be used as the cytotoxic agent in connection with the method of the present invention. It will be appreciated that antimitotic conjugates will kill retinal pigment epithelial cells while exhibiting less toxicity to the iris and corneal endothelium compared to ribosomal inhibitory proteins. A variety of known methods can be employed to conjugate the cytotoxin to the basement membrane binding agent. For example, the carboxyl groups of the cytotoxic agent can be attached to the amines of the basement membrane binding agent using a water-soluble carbodiimide technique. When this technique is used for conjugation, all of the conjugate will be internalized by the retinal pigment epithelial cells and the basement membrane binding agent will then be degraded by the cells to release the cytotoxic agent. Also, heterobifunctional crosslinkers, such as SPDP, can be used to conjugate the cytotoxic agent to the basement membrane binding agent, thereby creating a disulfide bond between the cytotoxic agent and the basement membrane binding agent. Once the resulting hybrid molecule has been internalized by the retinal pigment epithelial cell, the disulfide bond is hydrolyzed to release the cytotoxic agent, thus leading to the destruction of the cell. It is believed that recombinant DNA technology can also be used to construct the gene for a toxin with a basement membrane binding protein sequence incorporated therein. This gene can be expressed in a host cell and the purified product from the growth medium. By way of example, and not as limitation, a polylysine and saporin conjugate was prepared by coupling polylysine to SPDP according to the SPDP manufacturer's instructions. The free SPDP was then removed using a filtration technique, or, alternatively, through the use of a heparin sepharose co-column. The resulting polysillium-SPDP was then reduced with dithiothreitol. The saporin was then coupled with SPDP in the same manner and added to the polylysine-SPDP solution. The resulting solution was filtered to remove uncoupled agents, thus producing a solution of conjugated polylysine-saporin. The solution containing the basement membrane binding agent may consist of a variety of known biocompa-tibial agents. In one embodiment of the invention, the basement membrane binding agent is contained in a balanced salt solution. Solutions containing viscoelastic, such as methylcellulose, can also be used in connection with the present invention. It will be appreciated that other known biocompatible solutions can be used in connection with the method of the present invention. Although the present invention has been described herein with respect to certain preferred embodiments, one of ordinary skill in the relevant art will appreciate that various modifications can be made without departing from the intended spirit and scope of the invention.
Claims (56)
1. A method for destroying retinal pigment epithelial cells in a vitreous chamber of an eye after vitrectomy and retinal assembly, which method consists in: having a first solution containing a first basement membrane binding agent conjugated with a cytotoxic agent, introducing said first solution into said vitreous chamber, maintaining said first solution in said vitreous chamber for a predetermined period of time sufficient for said first basement membrane binding agent to attach to a basement membrane in said vitreous chamber and remove said basement membrane. first solution of said vitreous chamber, whereby the retinal pigment epithelial cells in said basement membrane within said vitreous chamber are exposed to said first base membrane binding agent conjugated to a cytotoxic agent, such that said epithelial cells retinal pigments internalize said first membrane binding agent Basal conjugate to a cytotoxic agent and whereby said retinal pigment epithelial cells are destroyed by said cytotoxic agent.
2. A method for destroying the retinal pigment epithelial cells in a vitreous chamber of an eye after vitrectomy and retinal assembly according to claim 1, wherein said first basement membrane binding agent is selected from a group consisting of: polylysine, fibronectin, laminin, type IV collagen, perle-cano, decorin, thrombospondin, tenascin, vitronectin, heparma, hepapna sulfate, poliargmam, dextran, dextran sulfate, chondroitme sulfate, hyaluronic acid, factor IV platelet, fibrin and fibrinogen.
3. A method for destroying the retimary pigment epithelial cells in a vitreous chamber after vi-trectomy and retinal assembly according to claim 2, wherein said first basement membrane binding agent is polylysine.
4. A method for destroying retinal pigment epithelial cells in a vitreous chamber after vi-trectomy and retinal assembly according to claim 1, wherein said cytotoxic agent is selected from a group consisting of: saporma, nema, methotrexate, 5- fluorouracil, daunomycin, doxorubicma, mitoxantrone, vinca alkaloids, vmblastma, colchicma, cytochamas, monensma and ouabain.
5. A method of killing retinal pigment epithelial cells in a vitreous chamber after vi-trectomy and retinal assembly according to claim 4, wherein said cytotoxic agent is selected from a group consisting of sapopne and nema.
6. A method for destroying retimary pigment epithelial cells in a vitreous chamber after vi-trectomy and retinal assembly according to claim 4, wherein said cytotoxic agent is saporma.
7. A method for destroying the retimary pigment epithelial cells in a vitreous chamber after vi-trectomy and retinal assembly according to claim 1, wherein said first solution consists of a balanced salt solution.
8. A method for destroying the retinal pigment epithelial cells in a vitreous chamber after vitrectomy and retinal assembly according to claim 1, wherein said first solution contains a viscoelastic material.
9. A method for destroying the retinal pigment epithelial cells in a vitreous chamber after vitrectomy and retinal assembly according to claim 1, wherein said cytotoxic agent is conjugated to said first basement membrane binding agent using a water-soluble carbodiimide technique.
10. A method for destroying the retinal pigment epithelial cells in a vitreous chamber after vitrectomy and retinal assembly according to claim 1, wherein said cytotoxic agent is conjugated to said first basement membrane binding agent using a hetero-bifunctional crosslinker.
11. A method for destroying the retinal pigment epithelial cells in a vitreous chamber after vitrectomy and retinal assembly according to claim 1, wherein said first basement membrane binding agent is polylysine and wherein said cytotoxic agent is saporin.
12. A method for destroying retinal pigment epithelial cells in a vitreous chamber after vitrectomy and retinal assembly according to claim 1, wherein said method further comprises: providing a second solution containing a second basement membrane binding agent, second basement membrane binding agent has a molecular weight greater than the molecular weight of said first base membrane binding agent; introducing said second solution into the basal membranes of the corneal endothelium within the vitreous chamber of said eye after removing said first solution from said eye, whereby said second basement membrane binding agent displaces said first basement membrane binding agent to the point that any first basal membrane binding agent has been attached to said basal membranes of the corneal endothelium, thus preventing the injury of said basal membranes of the corneal endothelium, and removing said second solution from said corneal endothelium.
13. A method for destroying the retinal pigment epithelial cells in a vitreous chamber after vitrectomy and retinal assembly according to claim 12, wherein said first basement membrane binding agent and said second basement membrane binding agent are polylysine.
14. A method for destroying retinal pigment epithelial cells in a vitreous chamber of an eye, which method consists in: having a first solution containing a first basal membrane binding agent, whose first basement membrane binding agent has a molecular weight; introducing said first solution in said eye before practicing a vitrectomy and reattaching the retina; maintaining said first solution in said eye for a predetermined period of time sufficient for said first basement membrane binding agent to attach to a basement membrane in the vitreous chamber of said eye; removing said first solution from said eye; practice a vitrectomy and a retina meeting; having a second solution containing a second basement membrane binding agent conjugated to a cytotoxic agent, which second basement membrane binding agent has a molecular weight; introducing said second solution into said video camera; maintaining said second solution in said vitreous chamber for a predetermined period of time sufficient for said second basement membrane binding agent to bind to a basement membrane in said vitreous chamber, and remove said second solution from said vitreous chamber, whereby the retinal pigment epithelial cells in said basement membrane inside said vitreous chamber are exposed to said second basement membrane binding agent conjugated to a cytotoxic agent, such that said pigment epithelial cells of the retina internalize said second agent of the retina. basement membrane binding conjugated to a cytotoxic agent and whereby said pigment epithelial cells of the retina are destroyed by said cytotoxic agent.
15. A method for destroying retinal pigment epithelial cells in a vitreous chamber of an eye according to claim 14, wherein said first basement membrane binding agent and said second basement membrane binding agent are selected from a group consisting of: polylysine, fibronectin , laminin, type IV collagen, perlecan, decorin, thrombospondin, tenascin, vitro-nectin, heparin, heparin sulfate, polyarginine, dextran, dextran sulfate, chondroitin sulfate, hyaluronic acid, platelet factor IV, fibrin and fibrinogen .
16. A method for destroying the retinal pigment epithelial cells in a vitreous chamber according to claim 15, wherein said first basement membrane binding agent and said second basement membrane binding agent are polylysine.
17. A method for destroying the retinal pigment epithelial cells in a vitreous chamber according to claim 16, wherein said molecular weight of said first basement membrane binding agent is greater than said molecular weight of said second basement membrane binding agent.
18. A method for destroying the retinal pigment epithelial cells in a vitreous chamber according to claim 14, wherein said cytotoxic agent is selected from a group consisting of: saporin, ricin, meto-trexate, 5-fluorouracil, daunomycin, doxorubicin, mito-xantrone, vinca alkaloids, vinblastine, colchicine, cytosine, monensin and ouabain.
19. A method for destroying the retinal pigment epithelial cells in a vitreous chamber according to claim 18, wherein said cytotoxic agent is selected from a group consisting of saporin and ricin.
20. A method for destroying the retinal pigment epithelial cells in a vitreous chamber according to claim 18, wherein said cytotoxic agent is saporin.
21. A method for destroying reticular pigment epithelial cells in a vitreous chamber according to claim 14, wherein said first solution and said second solution consist of a balanced salt solution.
22. A method for destroying the retimary pigment epithelial cells in a vitreous chamber according to claim 14, wherein said cytotoxic agent is conjugated to said second basement membrane binding agent using a water-soluble carbodiimide technique.
23. A method for destroying retimary pigment epithelial cells in a vitreous chamber according to claim 14, wherein said cytotoxic agent is conjugated to said second basement membrane binding agent using a hetero-bifunctional crosslinker.
24. A method for destroying retimary pigment epithelial cells in a vitreous chamber according to claim 14, wherein said second basal mem-brane binding agent is polylysine and wherein said cytotoxic agent is saporma.
25. A composition for killing retinal pigment epithelial cells in a vitreous chamber, consisting of a basement membrane binding agent conjugated to a cytotoxic agent.
26. A composition for destroying the reticular pigment epithelial cells in a vitreous chamber, consisting of polylys conjugated to a cytotoxic agent.
27. A composition for destroying retimary pigment epithelial cells in a vitreous chamber according to claim 25 or 26, wherein said cytotoxic agent is selected from a group consisting of saporin and ricin.
28. A composition for destroying the retinal pigment epithelial cells in a vitreous chamber according to claim 25 or 26, wherein said cytotoxic agent is saporin.
29. A composition for destroying proliferating cells in a vitreous chamber of an eye after reattaching the queen, which method consists in: providing a first solution containing a first basement membrane binding agent conjugated to a cytotoxic agent; introducing said first solution into said vitreous chamber; maintaining said first solution in said vitreous chamber for a predetermined period of time sufficient for said first basement membrane binding agent to attach to a basement membrane in said vitreous chamber, and remove said first solution from said vitreous chamber, whereby exposes the proliferating cells in said basement membrane within said vitreous chamber to said first basement membrane binding agent conjugated to a cytotoxic agent, such that said proliferating cells internalize said first basement membrane binding agent conjugated to a cytotoxic agent and whereby said proliferative cells are destroyed by said cytotoxic agent.
30. A method for destroying the proliferative cells in a vitreous chamber of an eye after reattaching the retina according to claim 29, wherein said first basement membrane binding agent is selected from a group consisting of: polylysine, fibronectin, laminin, collagen Type IV, perlecan, decorin, thrombospondin, tapeworm, vitronectin, heparin, heparin sulfate, poliar-ginin, dextran, dextran sulfate, chondroitin sulfate, hyaluronic acid, platelet factor IV, fibrin and fibrinogen.
31. A method for destroying the proliferative cells in a vitreous chamber after reattaching the retina according to claim 30, wherein said first basement membrane binding agent is polylysine.
32. A method for destroying the proliferative cells in a vitreous chamber after reattaching the retina according to claim 29, wherein said cytotoxic agent is selected from the group consisting of: saporin, ricin, methotrexate, 5-fluorouracil, daunomycin, doxorubicin , mitoxantrone, vinca alkaloids, vinblastine, colchicine, cytochasins, monensin and ouabain.
33. A method for destroying the proliferative cells in a vitreous chamber after vitrectomy and reattaching the retina according to claim 32, wherein said cytotoxic agent is selected from a group consisting of saporin and ricin.
34. A method for destroying the proliferative cells in a vitreous chamber after reattaching the retina according to claim 32, wherein said cytotoxic agent is saporin.
35. A method for destroying the proliferative cells in a vitreous chamber after reattaching the retina according to claim 29, wherein said first solution consists of a balanced salt solution.
36. A method for destroying the proliferative cells in a vitreous chamber after reattaching the retina according to claim 29, wherein said first solution contains a viscoelastic material.
37. A method for destroying the proliferating cells in a vitreous chamber after reattaching the retina according to claim 29, wherein said cytotoxic agent is conjugated to said first basement membrane binding agent using a water soluble carbodiimide technique.
38. A method for destroying the proliferative cells in a vitreous chamber after reattaching the retina according to claim 29, wherein said cytotoxic agent is conjugated to said first basement membrane binding agent using a hetero-bifunctional crosslinker.
39. A method for destroying the proliferative cells in a vitreous chamber after reattaching the retina according to claim 29, wherein said first basement membrane binding agent is polylysine and wherein said cytotoxic agent is saporin.
40. A method for destroying the proliferative cells in a vitreous chamber after reattaching the retina according to claim 29, wherein said method further comprises: disposing of a second solution containing a second basal membrane binding agent, the second of which basement membrane binding agent has a molecular weight greater than the molecular weight of said first basement membrane binding agent; introducing said second solution into the basal membranes of the corneal endothelium in the vitreous chamber of said eye after removing said first solution from said eye, whereby said second basement membrane binding agent displaces said first mem-brane binding agent. basal to the point that any first basal membrane binding agent has been attached to said basal membranes of the corneal endothelium, thus preventing the injury of said basal membranes of the corneal endothelium, and eliminating said second solution of said eye.
41. A method for destroying the proliferative cells in a vitreous chamber after reattaching the retina according to claim 40, wherein said first basement membrane binding agent and said second basement membrane binding agent are polylysine.
42. A method for destroying proliferating cells in a vitreous chamber of an eye, which method consists of: having a first solution containing a first basement membrane binding agent, whose first basement membrane binding agent has a molecular weight; introducing said first solution into said eye before reattaching the retina; maintaining said first solution in said eye for a predetermined period of time sufficient for said first basement membrane binding agent to attach to a basement membrane in the vitreous chamber of said eye; removing said first solution from said eye; reattach the retina; disposing of a second solution containing a second basement membrane binding agent conjugated to a cytotoxic agent, whose second ba-salt membrane binding agent has a molecular weight; introducing said second solution into said vitreous chamber; maintaining said second solution in said vitreous chamber for a predetermined period of time sufficient for said second basement membrane binding agent to bind to a basement membrane in said vitreous chamber, and remove said second solution from said vitreous chamber, whereby the proliferative cells of said basement membrane in said vitreous chamber are exposed to said second basement membrane binding agent conjugated to a cytotoxic agent, such that the proliferating cells internalize said second basement membrane binding agent conjugated to a cytotoxic agent and by which proliferating cells are destroyed by said cytotoxic agent.
43. A method for destroying proliferating cells in a vitreous chamber of an eye according to claim 42, wherein said first basement membrane binding agent and said second basement membrane binding agent are selected from a group consisting of: polylysine, fibronectin, laminin, type IV collagen, perlecan, decorin, trombobopondine, tenascin, vitronectin, heparin, heparin sulfate, polyarginine, dextran, dextran sulfate, chondroitin sulfate, hyaluronic acid, factor IV platelet, fibrin and fibrinogen.
44. A method for destroying proliferating cells in a vitreous chamber according to claim 43, wherein said first basement membrane binding agent and said second basement membrane binding agent are polylysine.
45. A method for destroying proliferating cells in a vitreous chamber according to claim 44, wherein said molecular weight of said first basement membrane binding agent is greater than said molecular weight of said second basement membrane binding agent.
46. A method for destroying the proliferating cells in a vitreous chamber according to claim 42, wherein said cytotoxic agent is selected from a group consisting of: saporin, ricin, methotrexate, 5-fluorouracil, daunomycin, doxorubicin, mitoxantrone, vinca alkaloids, vinblastine, colchicine , cytochasins, monensin and ouabain.
47. A method for destroying proliferating cells in a vitreous chamber according to claim 46, wherein said cytotoxic agent is selected from a group consisting of saporin and ricin.
48. A method for destroying the proliferative cells in a vitreous chamber according to claim 46, wherein said cytotoxic agent is saporin.
49. A method for destroying the proliferative cells in a vitreous chamber according to claim 42, wherein said first solution and said second solution consist of a balanced salt solution.
50. A method for destroying proliferating cells in a vitreous chamber according to claim 42, wherein said cytotoxic agent is conjugated to said second basement membrane binding agent using a water-soluble carbodiimide technique.
51. A method for destroying the proliferating cells in a vitreous chamber according to claim 42, wherein said cytotoxic agent is conjugated to said second basement membrane binding agent using a hetero-bifunctional crosslinker.
52. A method for destroying proliferating cells in a vitreous chamber according to claim 42, wherein said second basement membrane binding agent is polylysine and wherein said cytotoxic agent is saporin.
53. A composition for destroying the proliferating cells in a vitreous chamber, consisting of a basement membrane binding agent conjugated to a cytotoxic agent.
54. A composition for destroying proliferating cells in a vitreous chamber consisting of polylysine conjugated to a cytotoxic agent.
55. A composition for destroying proliferating cells in a vitreous chamber according to claim 53 or 54, wherein said cytotoxic agent is selected from a group consisting of saporin and ricin.
56. A composition for destroying proliferating cells in a vitreous chamber according to claim 53 or 54, wherein said cytotoxic agent is saporin. Summary A method to destroy pigment-retinal epithelial cells in an eye in order to prevent the appearance of proliferative vitreoretinopathy. A solution containing a basement membrane binding agent conjugated to a cytotoxic agent in the vitreous chamber is introduced. The solution is maintained in the vitreous chamber for a sufficient period of time to allow the basement membrane binding agent to bind to the basal membranes that line the vitreous chamber. The solution of the vitreous chamber is then removed, whereby a portion of the basement membrane binding agent remains attached to the basal membranes in the vitreous chamber, thus exposing the retinal pigment epithelial cells arranged in the basement membrane at cytotoxic agent.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US60/037994 | 1997-02-13 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MXPA99007449A true MXPA99007449A (en) | 2002-03-05 |
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