Methods for Diagnosing and Treating Eye-Length Related Disorders

Abstract

The invention provides to methods for diagnosing eye-length related disorders, including myopia. The invention also provides methods for treating and limiting eye-length related disorders, including myopia. In addition, the invention provides certain haplotypes associated with eye-length related disorders, including myopia and Bornholm Eye Disease.

What is claimed is: 
     
         1 . A method for determining the myopic potential of a patient comprising:
 testing a biological sample obtained from the patient to determine the L:M opsin gene haplotype of the patient; and   correlating the haplotype with a predicted spherical equivalent refraction.   
     
     
         2 . The method of  claim 1 , wherein the L:M opsin gene haplotype is a haplotype selected from the group consisting of:
 (i) (A) L-Opsin: methionine at position 153, isoleucine at position 171 and position 178, serine at position 180, and methionine at position 236; and (B) M-opsin: methionine at position 153, valine at position 171 and at position 178, and alanine at position 180;   (ii) (A) L-Opsin: methionine at position 153, valine at position 171, isoleucine at position 178, serine at position 180, and methionine at position 236; and (B) M-opsin: methionine at position 153, valine at position 171 and at position 178, and alanine at position 180;   (iii) (A) L-Opsin: leucine at position 153, valine at position 171, isoleucine at position 178, serine at position 180, and methionine at position 236; and (B) M-opsin: methionine at position 153, valine at position 171 and at position 178, and alanine at position 180;   (iv) (A) L-Opsin: methionine at position 153, valine at position 171, isoleucine at position 178, serine at position 180, and methionine at position 236; and (B) M-opsin: methionine at position 153, valine at position 171, isoleucine at position 178, and alanine at position 180;   (v) (A) L-Opsin: leucine at position 153, valine at position 171, isoleucine at position 178, alanine at position 180, and methionine at position 236; and (B) M-opsin: methionine at position 153, valine at position 171, isoleucine at position 178, and alanine at position 180;   (vi) (A) L-Opsin: methionine at position 153, valine at position 171, isoleucine at position 178, alanine at position 180, and methionine at position 236; and (B) M-opsin: methionine at position 153, valine at position 171, isoleucine at position 178, and alanine at position 180;   (vii) (A) L-Opsin: leucine at position 153, valine at position 171, isoleucine at position 178, serine at position 180, and methionine at position 236; and (B) M-opsin: leucine or methionine at position 153, valine at position 171, isoleucine at position 178, and alanine at position 180;   (viii) (A) L-Opsin: leucine at position 153, valine at position 171, isoleucine at position 178, serine at position 180, and methionine at position 236; and (B) M-opsin: methionine at position 153, valine at position 171, isoleucine at position 178, and alanine at position 180;   (ix) (A) L-Opsin: leucine at position 153, isoleucine at position 171, isoleucine at position 178, serine at position 180, and methionine at position 236; and (B) M-opsin: methionine at position 153, valine at position 171, valine at position 178, and alanine at position 180;   (x) (A) L-Opsin: methionine at position 153, valine at position 171, valine at position 178, alanine at position 180, and valine at position 236; and (B) M-opsin: methionine at position 153, valine at position 171, isoleucine at position 178, and alanine at position 180;   (xi) (A) L-Opsin: methionine at position 153, valine at position 171, isoleucine at position 178, serine at position 180, and valine at position 236; and (B) M-opsin: methionine at position 153, valine at position 171, valine at position 178, and alanine at position 180;   (xii) (A) L-Opsin: leucine at position 153, valine at position 171, isoleucine at position 178, serine at position 180, and methionine at position 236; and (B) M-opsin: leucine at position 153, valine at position 171, isoleucine at position 178, and serine at position 180; and   (xiii) (A) L-Opsin: leucine at position 153, valine at position 171, isoleucine at position 178, alanine at position 180, and methionine at position 236; and (B) M-opsin: leucine or methionine at position 153, valine at position 171, isoleucine at position 178, and alanine at position 180.   
     
     
         3 . The method of  claim 1 , wherein the testing comprises PCR amplification of the nucleic acids in the biological sample encoding one or more of amino acids 153, 171, 178, 180, and 236 of L-Opsin and one or more of amino acids 153, 171, 178, and 180 of M-Opsin. 
     
     
         4 . The method of  claim 3 , wherein the amplified nucleic acids are subjected to one or more procedures to detect the nucleotides selected from the group consisting of DNA sequence analysis, restriction digestion analysis, single strand conformation analysis. 
     
     
         5 . The method of  claim 3 , wherein the amplified nucleic acids are subjected to mass spectrometry to detect the nucleotides. 
     
     
         6 . The method of  claim 1 , further comprising the step of obtaining the L:M cone ratio in an eye of the patient; and wherein the correlating comprises correlating the L:M opsin gene haplotype and the L:M cone ratio with a predicted spherical equivalent refraction. 
     
     
         7 . A method for diagnosing susceptibility of a patient to an eye-length related disorder, the method comprising:
 obtaining a predicted spherical equivalent refraction; and   diagnosing the susceptibility of the patient to an eye-length related disorder based upon the predicted spherical refraction.   
     
     
         8 . The method according to  claim 7 , wherein the spherical equivalent fraction is predicted by:
 detecting in a biological sample comprising L-opsin and M-opsin nucleic acids obtained from the patient, the nucleotides encoding one or more of amino acids 153, 171, 178, 180, and 236 of L-opsin and the nucleotides encoding one or more of amino acids 153, 171, 178, and 180 of M-opsin;   determining the L:M opsin haplotype for the patient based upon the detected nucleotides; and   correlating the L:M opsin gene haplotype with a predicted spherical equivalent refraction.   
     
     
         9 . The method according to  claim 8 , wherein the L:M opsin haplotype is selected from the group consisting of: a particular combination of amino acids in the patient's L-Opsin gene or M-Opsin gene, wherein the patient is susceptible to an eye lengthening disorder if
 (i) (A) L-Opsin: methionine at position 153, isoleucine at position 171 and position 178, serine at position 180, and methionine at position 236; and (B) M-opsin: methionine at position 153, valine at position 171 and at position 178, and alanine at position 180;   (ii) (A) L-Opsin: methionine at position 153, valine at position 171, isoleucine at position 178, serine at position 180, and methionine at position 236; and (B) M-opsin: methionine at position 153, valine at position 171 and at position 178, and alanine at position 180;   (iii) (A) L-Opsin: leucine at position 153, valine at position 171, isoleucine at position 178, serine at position 180, and methionine at position 236; and (B) M-opsin: methionine at position 153, valine at position 171 and at position 178, and alanine at position 180;   (iv) (A) L-Opsin: methionine at position 153, valine at position 171, isoleucine at position 178, serine at position 180, and methionine at position 236; and (B) M-opsin: methionine at position 153, valine at position 171, isoleucine at position 178, and alanine at position 180;   (v) (A) L-Opsin: leucine at position 153, valine at position 171, isoleucine at position 178, alanine at position 180, and methionine at position 236; and (B) M-opsin: methionine at position 153, valine at position 171, isoleucine at position 178, and alanine at position 180;   (vi) (A) L-Opsin: methionine at position 153, valine at position 171, isoleucine at position 178, alanine at position 180, and methionine at position 236; and (B) M-opsin: methionine at position 153, valine at position 171, isoleucine at position 178, and alanine at position 180;   (vii) (A) L-Opsin: leucine at position 153, valine at position 171, isoleucine at position 178, serine at position 180, and methionine at position 236; and (B) M-opsin: leucine or methionine at position 153, valine at position 171, isoleucine at position 178, and alanine at position 180;   (viii) (A) L-Opsin: leucine at position 153, valine at position 171, isoleucine at position 178, serine at position 180, and methionine at position 236; and (B) M-opsin: methionine at position 153, valine at position 171, isoleucine at position 178, and alanine at position 180;   (ix) (A) L-Opsin: leucine at position 153, isoleucine at position 171, isoleucine at position 178, serine at position 180, and methionine at position 236; and (B) M-opsin: methionine at position 153, valine at position 171, valine at position 178, and alanine at position 180;   (x) (A) L-Opsin: methionine at position 153, valine at position 171, valine at position 178, alanine at position 180, and valine at position 236; and (B) M-opsin: methionine at position 153, valine at position 171, isoleucine at position 178, and alanine at position 180;   (xi) (A) L-Opsin: methionine at position 153, valine at position 171, isoleucine at position 178, serine at position 180, and valine at position 236; and (B) M-opsin: methionine at position 153, valine at position 171, valine at position 178, and alanine at position 180;   (xii) (A) L-Opsin: leucine at position 153, valine at position 171, isoleucine at position 178, serine at position 180, and methionine at position 236; and (B) M-opsin: leucine at position 153, valine at position 171, isoleucine at position 178, and serine at position 180; and   (xiii) (A) L-Opsin: leucine at position 153, valine at position 171, isoleucine at position 178, alanine at position 180, and methionine at position 236; and (B) M-opsin: leucine or methionine at position 153, valine at position 171, isoleucine at position 178, and alanine at position 180.   
     
     
         10 . The method of  claim 8 , wherein the detecting the nucleotides comprises PCR amplification of the nucleic acids encoding one or more of codons 153, 171, 178, 180, and 236 of L-Opsin and one or more of codons 153, 171, 178, and 180 of M-Opsin in the biological sample. 
     
     
         11 . The method of  claim 10 , wherein the amplified nucleic acids are subjected to one or more procedures to detect the nucleotides selected from the group consisting of DNA sequence analysis, restriction digestion analysis, and single strand conformation analysis. 
     
     
         12 . The method of  claim 10 , wherein the amplified nucleic acids are subjected mass spectrometry to detect the nucleotides. 
     
     
         13 . The method of  claim 8 , wherein the prediction of the spherical equivalent refraction further comprises obtaining the L:M cone ratio in an eye of the patient; and wherein the correlating comprises correlating the L:M opsin gene haplotype and the L:M cone ratio with a predicted spherical equivalent refraction. 
     
     
         14 . The method of  claim 7 , wherein the eye-length related disorder is myopia. 
     
     
         15 . A kit comprising an assay for detecting one or more of L:M opsin haplotypes, the kit comprising:
 a) one or more primer pairs selected from the group consisting of
 i) a primer pair for amplifying the nucleic acids encoding amino acid 153 of L-opsin, 
 ii) a primer pair for amplifying the nucleic acids encoding amino acid 171 of L-opsin, 
 iii) a primer pair for amplifying the nucleic acids encoding amino acid 178 of L-opsin, 
 iv) a primer pair for amplifying the nucleic acids encoding amino acid 180 of L-opsin, and 
 v) a primer pair for amplifying the nucleic acids encoding amino acid 236 of L-opsin; and 
   b) one or more primer pairs selected from the group consisting of
 i) a primer pair for amplifying the nucleic acids encoding amino acid 153 of M-opsin, 
 ii) a primer pair for amplifying the nucleic acids encoding amino acid 171 of M-opsin, 
 iii) a primer pair for amplifying the nucleic acids encoding amino acid 178 of M-opsin, and 
 iv) a primer pair for amplifying the nucleic acids encoding amino acid 180 of M-opsin.