Technology to detect early diabetic retinopathy

Yissum Research Development Company, the technology transfer arm of the Hebrew University of Jerusalem, has introduced a method for detecting retinal micro-aneurysms that potentially pose a high risk for leakage of blood and blood products, which can lead to visual impairment in diabetic retinopathy (amongst other retinal vascular diseases). This method is likely to enable early diagnosis and treatment of the condition, potentially minimizing damage and saving vision. 

The technology has been patented by Yissum and is currently searching for an appropriate partner for the further development and commercialization of the invention. 

Dr. Yaakov Nahmias and his team from the Center for Bioengineering at the Hebrew University of Jerusalem developed a computational method to identify microvascular regions with high risk of leakage based on fluid dynamics. The method will enable ophthalmologists to identify microaneurysms with a high risk of leakage using adaptive optics. The scientists found that high risk is correlated with increased level of a protein called Von Willebrand factor (vWF), which has been associated with early development of diabetic retinopathy.

Retinal microaneurysms are dilations of small blood vessels in the retina, and an early feature of diabetic retinopathy, one of the leading causes of blindness worldwide. Retinal microaneurysms reduce vision because they eventually cause fluid leakage from blood vessels and retinal edema. Localized leakage can be detected and treated using laser ablation slowing the progression of diabetic blindness.

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Stem cells for treating Diabetic Retinopathy

An article, recently published in the PLOS, refers to pericytes derived from adipose-derived (or in lay terms, fat-derived) stem cells (ASCs), being able to integrate with retinal vasculature, and providing functional vascular protection in animal models.

(c) Robert M Hunt

Pericytes are contractile cells that wrap around endothelial cells of capillaries and venules throughout the body. These cells regulate capillary blood flow, the clearance and phagocytosis of cellular debris, and the permeability of the blood-retinal barrier. A deficiency of pericytes can cause the barrier to break down, leading to leakage of blood and other products.

Diabetic individuals often exhibit loss of pericytes in their retina. This is a characteristic sign early on in the disease. These cells are important for the protection of endothelial cells in the retina. With their loss, microaneuryms form in the capillaries, which is the earliest clinical sign of diabetic retinopathy.

ASCs have been found to differentiate into pericytes, which suggests they may be useful as protective and regenerative cellular therapy for retinal vascular disease.

The PLOS study was undertaken by Thomas A Mendel and his colleagues, a majority of whom are from University of Virginia, Charlottesville. They found that when ASCs were injected intravitreally (inside the eye) into a murine eye subjected to oxygen-induced retinopathy (OIR) (which resembles diabetic retinopathy), the cells were capable of migrating to and integrating with the retinal vasculature. ASCs injected after OIR vessel destabilization and ablation enhanced vessel regrowth (16% reduction in avascular area). ASCs injected intravitreally before OIR vessel destabilization prevented more than 50% of retinal capillary dropout (which is commonly seen in patients with diabetic retinopathy). . Injected ASCs also prevented capillary loss in the diabetic retinopathic mouse model (79% reduction observed 2 months after injection).

The authors have concluded that ASC-derived pericytes can integrate with retinal vasculature, adopting both pericyte morphology and marker expression, and provide functional vascular protection in multiple animal models of retinal vasculopathy. The pericyte phenotype demonstrated by ASCs is enhanced with additional (TGF-β1) treatment, as seen with native retinal pericytes. 

The authors feel that ASCs may represent an innovative cellular therapy for protection against and repair of diabetic retinopathy and other retinal vascular diseases.