Gap junction intercellular communication modulators and their use for the treatment of diabetic eye disease
The use of gap junction intercellular communication (GJIC) modulators in the treatment or prevention of diabetic eye disease is disclosed, and more particularly to their use for the treatment or prevention of early stage diabetic retinopathy and diabetic macular edema by inhibiting apoptosis of retinal endothelial cells and inhibiting pericyte loss.
1. A method of treating early stage diabetic eye disease or diabetic macular edema in a human subject, the method comprising administering to the human subject a therapeutically effective amount of the compound, or a pharmaceutically acceptable salt or hydrate thereof, wherein the compound is selected from the group consisting of:
(2S,4R)-1-(2-aminoacetyl)-4-benzoylamino-pyrrolidine-2-carboxylic acid; and
Ac-DTyr-DPro-DHyp-Gly-DAla-Gly-NH 2 ;
or a pharmaceutically acceptable salt or hydrate thereof.
2. The method of treatment according to claim 1 , wherein the compound is (2S,4R)-1-(2-aminoacetyl)-4-benzoylamino-pyrrolidine-2-carboxylic acid, or a pharmaceutically acceptable salt or hydrate thereof.
3. The method of treatment according to claim 1 , wherein the method is for the prevention of early stage diabetic retinopathy or diabetic macular edema in a human subject.
4. The method of treatment according to claim 1 , wherein the diabetic retinopathy is mild non-proliferative retinopathy or moderate non-proliferative retinopathy in a human subject.
5. The method of treatment according to claim 1 , wherein the compound is for use in treating or preventing diabetic macular edema.
6. The method of treatment or prevention according to claim 1 , wherein the compound is for preventative treatment of a patient with a chronically high blood glucose level as the patient is brought into glycaemic control.
7. The method of treatment according claim 1 , wherein the compound inhibits pericyte loss in the retina.
8. The method of treatment according to claim 1 , wherein the compound inhibits vascular leakage in the retina.
9. The method of treatment according to claim 1 , wherein the compound inhibits apoptosis of retinal endothelial cells.
10. The method of treatment according to claim 1 , wherein the patient has type 1 diabetes, type 2 diabetes or gestational diabetes.
11. The method of treatment according to claim 3 , wherein the method prevents a progression of early stage diabetic retinopathy or diabetic macular edema in a human subject to mild non-proliferative retinopathy or moderate non-proliferative retinopathy.
12. The method of treatment according to claim 4 , wherein the method prevents a progression of mild non-proliferative retinopathy or moderate non-proliferative retinopathy in a human subject to severe non-proliferative retinopathy.