COMPOSITIONS AND METHODS FOR REDUCING RISK OF DEVELOPMENT, OR SEVERITY, OF INAPPROPRIATE IMMUNE RESPONSE IN EYES
A composition for reducing the risk of development, or severity, of an inappropriate immune response in an eye comprises an antagonist to at least a human TLR, an antagonist to at least a coreceptor of human TLR, a compound that is capable of inhibiting an activation of a human TLR signaling pathway, or a combination thereof. The composition can be used to reduce the risk of development, or severity, of contact lens-associated corneal infiltrates. The composition can be formulated into an eye drop or a contact lens-treating, -storing, -cleaning, -disinfecting, or -wetting solution.
1 . A composition comprising an antagonist to at least a human TLR, an antagonist to at least a coreceptor of human TLR, a compound that is capable of inhibiting an activation of a human TLR signaling pathway, or a combination thereof; wherein said antagonist, compound, or combination thereof is present at a concentration such that the composition is capable of reducing a risk of development, or severity, of an inappropriate immune response in an eye.
2 . The composition of claim 1 , wherein the inappropriate immune response in an eye comprises contact lens-associated corneal infiltrates (“CLACIs”).
3 . The composition of claim 2 , wherein the composition comprises a contact lens-treating, -storing, -cleaning, -disinfecting, or -wetting solution.
4 . The composition of claim 1 , wherein said at least a human TLR is selected from the group consisting of TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR10, and combinations thereof.
5 . The composition of claim 1 , wherein said at least a coreceptor of human TLR comprises CD14, MD-2, a combination thereof, or a mixture thereof.
6 . The composition of claim 1 , wherein said antagonist or said compound is selected from the group consisting of anti-human antibodies of TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR10, CD14, or MD-2; and combinations thereof.
7 . The composition of claim 1 , wherein said compound that is capable of inhibiting an activation of a human TLR signaling pathway comprises a soluble form of an extracellular domain of a human TLR that recognizes a microbe-expressed molecular structure.
8 . The composition of claim 1 , wherein said compound that is capable of inhibiting an activation of a human TLR signaling pathway comprises at least a soluble form of CD14 or MD-2.
9 . The composition of claim 1 , wherein said antagonist or compound comprises a nucleotide sequence selected from the group consisting of SEQ. NO. 1-SEQ. NO. 8, and combinations thereof.
10 . The composition of claim 1 , wherein said antagonist or compound comprises a nucleotide sequences comprising multiple repeats of any one of SEQ. NO. 1-SEQ. NO. 8.
11 . The composition of claim 10 , wherein said nucleotide sequence comprises two, three, four, or five repeats of any one of SEQ. NO. 1-SEQ. NO. 8.
12 . The composition of claim 1 , wherein said antagonist or compound comprises a material selected from the group consisting of chloroquine, hydroxychloroquine, quinacrine, 9-aminoacridine, 4-aminoquinoline, and a mixture thereof.
13 . The composition of claim 1 , wherein said antagonist or compound comprises a ligand of vitamin D receptor.
14 . The composition of claim 13 , wherein said ligand of vitamin D receptor comprises vitamin D or an analogue thereof.
15 . The composition of claim 13 , wherein said ligand of vitamin D receptor comprises vitamin D 2 , vitamin D 3 , or a mixture thereof.
16 . The composition of claim 1 , wherein said antagonist or said compound is present in an amount in a range from about 0.0001 to about 5 percent by weight of said composition.
17 . The composition of claim 6 , wherein said antagonist or said compound is present in an amount in a range from about 0.001 to about 2 percent by weight of said composition.
18 . The composition of claim 16 , further comprising a material selected from the group consisting of carriers, preservatives, antimicrobial agents, surfactants, buffers, tonicity-modifying agents, chelating agents, viscosity-modifying agents, co-solvents, oils, humectants, emollients, stabilizers, antioxidants, and combinations thereof.
19 . The composition of claim 18 , wherein the composition has a pH in a range from about 5 to about 8.
20 . The composition of claim 18 , wherein the composition has a pH in a range from about 6.5 to about 7.8.
21 . A composition comprising an antagonist to at least a human TLR, an antagonist to at least a coreceptors of human TLR, a compound that is capable of inhibiting an activation of a human TLR signaling pathway, or a combinations thereof; wherein the composition is capable of reducing a risk of development, or severity, of an inappropriate immune response in an eye; wherein said at least a human TLR comprises TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR10, or a combination thereof; said at least a coreceptors of human TLR comprises CD14, MD-2, a combination thereof, or a mixture thereof; said antagonist or compound is present in an amount from about 0.0001 to about 5 percent by weight of said composition; and said composition has a pH of about 5-8.
22 . A method for reducing risk of development, or severity, of an inappropriate immune response in an eye of a subject, the method comprising transferring to an environment of said eye a composition that comprises an antagonist to at least a human TLR, an antagonist to at least a coreceptor of human TLR, a compound that is capable of inhibiting an activation of a human TLR signaling pathway, or a combination thereof.
23 . The method of claim 22 , wherein said transferring comprising administering a pharmaceutically effective amount of said composition to said eye.
24 . The method of claim 23 , wherein said amount is effective to reduce the risk of development, or severity, of the inappropriate immune response in the eye.
25 . The method of claim 22 , wherein said inappropriate immune response comprises CLACIs.
26 . The method of claim 25 , wherein said transferring comprising contacting a contact lens to be worn by said subject with said composition before installing said contact lens in said subject.
27 . The method of claim 26 , wherein the composition comprises a contact lens-treating, -storing, -cleaning, -disinfecting, or -wetting solution.
28 . The method of claim 25 ; wherein said at least a human TLR comprises TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR10, or a combination thereof; and said at least a coreceptor of human TLR comprises CD14, MD-2, a combination thereof, or a mixture thereof.
29 . The method of claim 25 , wherein said antagonist or said compound is selected from the group consisting of anti-human antibodies of TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR10, CD14, or MD-2; and combinations thereof.
30 . The method of claim 25 , wherein said compound that is capable of inhibiting an activation of a human TLR signaling pathway comprises a soluble form of an extracellular domain of a human TLR that recognizes a microbe-expressed molecular structure, or a soluble form of CD14 or MD-2.
31 . The method of claim 25 , wherein said antagonist or compound comprises a nucleotide sequence selected from the group consisting of SEQ. NO. 1-SEQ. NO. 8, and combinations thereof.
32 . The method of claim 25 , wherein said antagonist or compound comprises a nucleotide sequences comprising multiple repeats of any one of SEQ. NO. 1-SEQ. NO. 8.
33 . The method of claim 32 , wherein said nucleotide sequence comprises two, three, four, or five repeats of any one of SEQ. NO. 1-SEQ. NO. 8.
34 . The method of claim 25 , wherein said antagonist or compound comprises a material selected from the group consisting of chloroquine, hydroxychloroquine, quinacrine, 9-aminoacridine, 4-aminoquinoline, and a mixture thereof.
35 . The method of claim 25 , wherein said antagonist or compound comprises a ligand of vitamin D receptor.
36 . The method of claim 35 , wherein said ligand of vitamin D receptor comprises vitamin D or an analogue thereof.
37 . The method of claim 35 , wherein said ligand of vitamin D receptor comprises vitamin D 2 , vitamin D 3 , or a mixture thereof.
38 . The method of claim 25 , wherein said antagonist or said compound is present in an amount in a range from about 0.0001 to about 5 percent by weight of said composition.
39 . A method for reducing a risk of development, or severity, of CLACIs in a subject, the method comprising contacting a contact lens to be worn by the subject with a composition before installing the contact lens in the subject; wherein the composition comprises an antagonist to at least a human TLR, an antagonist to at least a coreceptor of human TLR, a compound that is capable of inhibiting an activation of a human TLR signaling pathway, or a combination thereof; wherein the composition is capable of reducing said risk; and wherein said at least a human TLR comprises TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR10, or a combination thereof; said at least a coreceptor of human TLR comprises CD14, MD-2, a combination thereof, or a mixture thereof; said antagonist or compound is present in an amount from about 0.0001 to about 5 percent by weight of said composition; and said composition has a pH of about 5-8.
40 . A method for reducing a risk of development, or severity, of CLACIs in a subject, the method comprising transferring an amount of a composition to an eye of the subject; wherein the composition comprises an antagonist to at least a human TLR, an antagonist to at least a coreceptor of human TLR, a compound that is capable of inhibiting an activation of a human TLR signaling pathway, or a combination thereof; wherein the amount is effective to reduce said risk; and wherein said at least a human TLR comprises TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR10, or a combination thereof, said at least a coreceptor of human TLR comprises CD14, MD-2, a combination thereof, or a mixture thereof; said antagonist or compound is present in an amount from about 0.0001 to about 5 percent by weight of said composition; and said composition has a pH of about 5-8.
41 . A method for preparing an ophthalmic composition, the method comprising: (a) combining an antagonist to at least a human TLR, an antagonist to at least a coreceptor of human TLR, a compound that is capable of inhibiting an activation of a human TLR signaling pathway, or a combination thereof with an ophthalmically acceptable carrier to form said ophthalmic composition; wherein said antagonist or said compound is present in said composition in a concentration such that an effective amount can be transferred to a corneal environment of a subject.