Methods and pharmaceutical compositions for the treatment of retinal capillary non-perfusion

A method of treating a subject suffering from or suspected of having retinal capillary non-perfusion comprising

• administering locally to the subject a therapeutically effective amount of a Rho-associated protein kinase (ROCK) inhibitor to cells of a retinal pigment epithelium (RPE),
• wherein the ROCK inhibitor is administered in an amount sufficient to reduce retinal vascular endothelial growth factor (VEGF) expression and occurrence of endothelial cell intraluminal blebbing, to at least partially restore outer blood-retinal barrier function of the RPE, and to inhibit or reduce vessel leakage through the RPE,
• wherein the administering step is performed prior to development of irreversible retinal damage, and
• wherein administration is intravitreous,
• wherein the retinal capillary non-perfusion is secondary to preclinical diabetic retinopathy, and
• wherein the retinal capillary non-perfusion is not secondary to retinal vein occlusion.

A method of inhibiting retinal capillary non-perfusion in a subject suffering from a disruption of an outer blood-retinal barrier, comprising

• administering intravitreously to the subject a therapeutically effective amount of a Rho-associated protein kinase (ROCK) inhibitor to retinal pigment epithelial cells,
• wherein the ROCK inhibitor is sufficient to inhibit or reduce loss of tight junctions between cells of a retinal pigment epithelium layer and/or to inhibit loss of the outer blood-retinal barrier function;
• and
• wherein the administering step is performed prior to development of retinal ischemia, and wherein the therapeutically effective amount of ROCK inhibitor reduces expression of retinal vascular endothelial growth factor and inhibits endothelial cell intraluminal blebbing;
• wherein the administering step is performed prior to development of irreversible retinal damage secondary to diabetic retinopathy;
• and
• wherein the retinal capillary non-perfusion is not secondary to retinal vein occlusion.

A method of inhibiting retinal capillary non-perfusion in a subject suffering from preclinical diabetic retinopathy, comprising

• administering intravitreously to the subject a therapeutically effective amount of a Rho-associated protein kinase (ROCK) inhibitor to retinal pigment epithelial cells, wherein the ROCK inhibitor is the only active agent that is administered,
• wherein the ROCK inhibitor is sufficient to inhibit or reduce endothelial cell intraluminal blebbing, loss of tight junctions between cells of a retinal pigment epithelium layer and/or to inhibit loss of the outer blood-retinal barrier function;
• and
• wherein the administering step is performed prior to onset of diabetic retinopathy.