The effect of intravitreally administered angiogenesis inhibitor on the concentration of angiotensin-converting enzyme in the blood serum and lacrimal fluid in patients with diabetic macular edema

Abstract

BACKGROUND: Diabetic retinopathy (DR) is one of the more serious complications of diabetes and the main cause of blindness among working-age individuals. In recent years, information has emerged on the possible role of the renin-angiotensin system (RAS) in the pathogenesis of DR, and DRs possible connection with the system of pro-angiogenic factors.
 AIM: To study the impact of anti-angiogenic therapy on systemic and local concentrations of angiotensin-converting enzyme (ACE), a key component of RAS, for patients with diabetic macular edema (DME).
 MATERIAL AND METHODS: The concentration of ACE in the lacrimal fluid and blood serum in 10 patients (20 eyes) with DME was determined before and after intravitreal injection (IVI) of ranibizumab. The comparison group consisted of 7 patients (14 eyes) with age-related macular degeneration (AMD). The control group consisted of 10 healthy individuals (20 eyes). All groups were comparable in age and sex. The concentration of ACE was determined by enzyme immunoassay. The main group was examined four times: before IVI of ranibizumab, and then one week, two weeks and one month after IVI of ranibizumab. The comparison group was examined before, and then one week after, IVI of ranibizumab.
 RESULTS: In patients with DME, there was an initial 1.8-fold increase in the concentration of ACE in the lacrimal fluid of both eyes. A week after IVI of ranibizumab, the concentration of ACE in the lacrimal fluid began to decrease, reaching the control level after two weeks, and remaining there one month after IVI of ranibizumab. Initially, the concentration of ACE in the blood serum in patients with DME was 2.2 times lower than the control level. After IVI of ranibizumab there was an increase in the concentration of ACE in the blood serum, but by the end of the observation, the indicators continued to remain well below the control level. In patients with AMD, the initial concentration of ACE in the lacrimal fluids was not elevated; the concentration of ACE in the lacrimal fluids decreased 1.4 times one week after IVI of ranibizumab. The concentration of ACE in the blood serum of the patients with AMD was initially 25% lower than the control level, and essentially did not change after IVI of ranibizumab.
 СONCLUSIONS: Changes in the concentration of ACE in patients with DME may be a new prognostic criterion for the development of DME for patients with diabetes. These changes in the concentration of ACE, in the context of antiangiogenic therapy, indicate an interaction between the renin-angiotensin and angiogenic systems. Similar changes that were observed after IVI of ranibizumab in patients with AMD confirm the mutual influence of these two systems.
 The data presented in this study open up prospects for finding new pathways of pathogenic therapy for diabetic macular edema and diabetes.

Variation of Concentrations of Angiotensin II, AngiotensinConverting Enzyme and Matrix Metalloprotease-9 in Tears and Serum of Patients with Diabetic Retinopathy

“…Кроме того, следует учитывать, что в роговице и в конъюнктиве содержится АПФ [16], а при ДР имеет место повышенная проницаемость сосудов, в том числе и сосудов конъюнктивы, что тоже может приводить к повышению концентрации данного показателя. Полученные данные согласуются с результатами ранее выполненных нами работ, которые показали повышение активности АПФ в СЖ при прогрессировании ДР [22,23], двукратное повышение концентрации АПФ в СЖ у пациентов с диабетическим макулярным отеком [24].…”