Diabetic Retinopathy

Retinopathy affects approximately 30% of patients with diabetes and is a serious threat to vision. Diabetic retinopathy is the leading cause of new blindness in adults, and is the underlying cause of approximately 20% of new blindness diagnosed in the United States each year. Diabetic retinopathy results from damage to the circulatory system of the retina, affects both eyes similarly and progresses through two phases:

• Non-proliferative retinopathy: This phase initially manifests as leakiness and weakness of the retinal vessels. Small bulges (microaneurysms) protrude from the walls of the retinal capillaries, which can ooze fluid and blood into the retina. With progression, other signs of damage include patches of swollen nerve fibers, swelling of retinal veins, closure of vessels and development of proliferative retinopathy.
• Proliferative retinopathy: This phase is characterized by the growth on the retina of new rogue vessels which are fragile and prone to hemorrhage, leaking blood into the retina and vitreous and causing retinal tears and detachment, formation of scar tissue and neovascular glaucoma. Closure of capillaries supplying blood to the light-concentrating central portion of the retina and swelling (macular edema), which severely compromise vision, can develop at all phases of retinopathy.

The main treatment modalities for diabetic retinopathy entail laser photocoagulation for macular edema and severe non-proliferative and proliferative disease, and surgical removal of blood (vitrectomy) and scar tissue. Timely laser photocoagulation and vitrectomy can reduce the risk for visual loss but do not cure the underlying disease. Many patients with vision-threatening retinopathy are without symptoms until late stages, and diabetic retinopathy remains a serious medical problem with no approved drug therapy.

In preclinical studies, GLY-230 has been shown to restore the balance between proangiogenic and anti-angiogenic factors in ocular fluid, and to reduce products of oxidative stress. A717, Glycadia’s monoclonal antibody, significantly improved retinal capillary pathology in preclinical studies.

Diabetic Retinopathy References

Investigative Ophthalmology & Visual Science 42:1660-1668, 2001:
Signaling pathways for glycated human serum albumin-induced IL-8 and MCP-1 secretion in human RPE cells.

Ophthalmic Research 40:5-9, 2008:
Vitreous fluid of db/db mice exhibits alterations in angiogenic and metabolic factors consistent with early diabetic retinopathy.

Investigative Ophthalmology & Visual Science 49:5089-5093 2008:
Amelioration of diabetes-associated abnormalities in the vitreous fluid by an inhibitor of albumin glycation.

Biochim Biophys Acta 1830:5480-5485, 2013:
Clinical, pathophysiological and structure/function consequences of modification of albumin by Amadori-glucose adducts