Methods and Compositions for Treating Conditions of the Eye

Abstract

Provided are methods and compositions for the photodynamic therapy (PDT) of ocular conditions characterized by the presence of unwanted choroidal neovasculature, for example, neovascular age-related macular degeneration. The selectivity and sensitivity of the PDT method can be enhanced by combining the PDT with an anti-angiogenesis factor, for example, angiostatin or endostatin, or with an apoptosis-modulating factor. Furthermore, the selectivity and sensitivity of the PDT may be further enhanced by coupling a targeting moiety to the photosensitizer so as to target the photosensitizer to choroidal neovasculature.

1 - 19 . (canceled) 
     
     
         20 . A method of treating unwanted choroidal neovasculature in a mammal, the method comprising the steps of:
 (a) administering to the mammal, an apoptosis-inducing factor in an amount sufficient to permit an effective amount to localize in the choroidal neovasculature or tissue surrounding the choroidal neovasculature;   (b) administering to the mammal an amount of photosensitizer sufficient to permit an effective amount to localize in the choroidal neovasculature; and   (c) irradiating the choroidal neovasculature with laser light such that the light is absorbed by the photosensitizer so as to occlude the choroidal neovasculature, wherein the level of cell damage to the choroidal neovasculature relative to the tissue surrounding the choroidal neovasculature resulting from steps (a), (b) and (c) is greater than that resulting from steps (b) and (c) alone.   
     
     
         21 . The method of  claim 20 , wherein the mammal is a primate. 
     
     
         22 . The method of  claim 20 , wherein the mammal is a human. 
     
     
         23 . The method of  claim 20 , wherein the apoptosis-inducing factor is administered to the mammal before administration of the photosensitizer. 
     
     
         24 . The method of  claim 20 , wherein the photosensitizer is an amino acid derivative, an azo dye, a xanthene derivative, a chlorin, a tetrapyrrole derivative, or a phthalocyanine. 
     
     
         25 . The method of  claim 20 , wherein the photosensitizer is lutetium texaphyrin, a benzoporphyrin, a benzoporphyrin derivative, a hematoporphyrin or a hematoporphyrin derivative. 
     
     
         26 . (canceled) 
     
     
         27 . The method of  claim 20 , wherein the apoptosis-inducing factor is a protein or peptide capable of inducing apoptosis in cells disposed in the choroidal neovasculature. 
     
     
         28 . The method of  claim 27 , wherein the protein or peptide selectively binds to neovasculature. 
     
     
         29 . (canceled) 
     
     
         30 . The method of  claim 27 , wherein the peptide comprises an amino acid sequence comprising, in an N- to C-terminal direction, KLAKLAKKLAKLAK (SEQ. ID. NO 1). 
     
     
         31 . The method of  claim 30 , wherein the peptide further comprises an RGD-4C peptide sequence. 
     
     
         32 . The method of  claim 20 , wherein the method ameliorates the symptoms of a disorder selected from the group consisting of age-related macular degeneration, ocular histoplasmosis syndrome, pathologic myopia, angioid streaks, idiopathic disorders, choroiditis, choroidal rupture, overlying choroid nevi, and inflammatory diseases. 
     
     
         33 . The method of  claim 32 , wherein the disorder is age-related macular degeneration. 
     
     
         34 . The method of  claim 20 , wherein the apoptosis-inducing factor is administered to the mammal before the irradiation. 
     
     
         35 . The method of  claim 20 , wherein the apoptosis-inducing factor and the photosensitizer are administered simultaneously. 
     
     
         36 . The method of  claim 20 , wherein the apoptosis-inducing factor is angiostatin, constantin, TNF α, a bioactive fragment of TNF α, cycloheximide, tunicamyicin, or adenosine. 
     
     
         37 . The method of  claim 36 , wherein the apoptosis-inducing factor is angiostatin. 
     
     
         38 . The method of  claim 36 , wherein the apoptosis-inducing factor is TNF-alpha. 
     
     
         39 . The method of  claim 20 , wherein the apoptosis-inducing factor is an antisense nucleic acid or peptidyl nucleic acid that reduces or turns off the expression of a death antagonist. 
     
     
         40 . The method of  claim 39 , wherein the death antagonist is Bcl- 2  or Bcl-x L .