Methods for the treatment and prevention of age-related retinal dysfunction
A method of treating or preventing age-related retinal dysfunction involves administering to a patient a pharmaceutically effective amount of a synthetic retinal derivative repeatedly over a duration of at least about 3 months. Effective synthetic retinal derivatives include 9-cis-retinyl esters, 11-cis-retinyl esters, derivatives and congeners thereof, and combinations thereof. Suitable ester substituents include carboxylates of C 1 -C 10 monocarboxylic acids and C 2 -C 22 polycarboxylic acids.
1. A method of treating age-related impairment in rod-mediated dark adaptation after light exposure in a human subject in need thereof, comprising:
administering a therapeutically effective amount of a synthetic retinal derivative to the human subject, wherein the synthetic retinal derivative supplements or replaces endogenous 11-cis-retinal in the eye, wherein the synthetic retinal derivative is administered orally as a long term dosage regimen about once every other day to about once a month for about four months or longer; and wherein the synthetic retinal derivative has a structure represented by Formula I:
wherein A is CH 2 OR, and wherein R is the ester forming portion of a C 1 to C 10 monocarboxylic acid or a C 2 to C 22 polycarboxylic acid.
2. The method of claim 1 , wherein the synthetic retinal derivative is administered about once a month over a period of at least four months.
3. The method of claim 1 , wherein the synthetic retinal derivative is administered about 2-4 times per week to about once every month for at least four months or longer.
4. The method of claim 1 , wherein the ester substituent is a carboxylate radical of a polycarboxylic acid of C 3 to C 10 .
5. The method of claim 1 , wherein the synthetic retinal derivative is 9-cis-retinyl acetate, 9-cis-retinyl succinate, 9-cis-retinyl citrate, 9-cis-retinyl ketoglutarate, 9-cis-retinyl fumarate, 9-cis-retinyl malate or 9-cis-retinyl oxaloacetate.
6. The method of claim 5 , wherein the synthetic retinal derivative is contained within a pharmaceutically acceptable vehicle, wherein the pharmaceutically acceptable vehicle is vegetable oil.
7. The method of claim 1 , wherein the synthetic retinal derivative is 9-cis-retinyl acetate or 9-cis-retinyl succinate.
8. The method of claim 1 , wherein the synthetic retinal derivative is administered at an individual dosage greater than an effective daily dose.
9. The method of claim 1 , wherein the synthetic retinal derivative is administered at a dose of about 0.1 to about 1000 mg.
10. The method of claim 3 , wherein the synthetic retinal derivative is administered about once every two weeks over a period of at least four months.
11. The method of claim 1 , wherein the synthetic retinal derivative is administered at a dose of about 0.01 to about 10 mg/kg body weight of the human subject.
12. The method of claim 11 , wherein the synthetic retinal derivative is administered at a dose of about 0.05 to about 7.5 mg/kg body weight of the human subject.
13. The method of claim 12 , wherein the synthetic retinal derivative is administered at a dose of about 0.1 to about 5 mg/kg body weight of the human subject.
14. The method of claim 13 , wherein the synthetic retinal derivative is administered at a dose of about 0.1 to about 1 mg/kg body weight of the human subject.