Diabetic retinopathy (DR) is one of the most significant microvascular complications of diabetes mellitus (DM) and is the most common cause of blindness in people under the age of 65. The ability to accurately predict patient susceptibility and prognostic implications of the disease is essential to its optimal management. Unfortunately, the current screening process for DR restricts the population that can be evaluated and the disease goes undetected until irreversible damage occurs. Therefore, a reliable and inexpensive screening process for DR would greatly increase the number of patients that can be evaluated and identify individuals in the early stages of DR in need of further assessment and treatment. Our previous work has shown that elevated blood homocysteine (Hcy) levels disrupted blood retinal barrier integrity, induced retinal ischemia and neovascularization, activated endoplasmic reticulum and oxidative stress pathways and induced epigenetic modifications in the retina. The current study aimed to evaluate Hcy as a biomarker in DR screening. Hcy levels were measured by ELISA and immunolocalization methods in serum, vitreous and retina of diabetic patients as well as in serum and retina of different animal models of DM representing type 1 diabetes (T1DM) (STZ mice, Akita mice and STZ rats) and db/db mice which exhibit features of human type 2 diabetes (T2DM). Our results revealed increased Hcy levels and immunostaining in serum, vitreous and retina of diabetic patients and experimental animals’ models of diabetes. Moreover, optical coherence tomography (OCT) and fluorescein angiography (FA) were used to evaluate the retinal changes in mice eyes after Hcy-intravitreal injection into the eyes of normal wild type (WT) and diabetic (STZ) mice. Hcy-induced changes in mice retina which were aggravated under diabetic conditions.
In conclusion, our data reported Hcy as a strong candidate for use as a biomarker in DR screening. Furthermore, targeting Hcy clearance could be a future therapeutic target for DR.
A.M. Tawfik: None. R. Mohamed: None. S. Alhusban: None. S.M. Chu: None. A.Q. Khalil: None. M. Bartolli: None. M. Al-Shabrawey: None.
American Heart Association (16SDG30700016)