Título

ROLE OF ANXA1 IN DIABETIC RETINOPATHY AND ANGIOGENESIS

Objetivo

The objective was to investigate the role of AnxA1 in the pathogenesis of diabetic retinopathy and angiogenesis.

Método

AnxA1 +/+ and AnxA1 -/- mice were used to induce DR over a 12-week period using
streptozotocin administration. Body weight and blood glucose levels were monitored. Western blotting evaluated the expression GFAP and vimentin, GS and cleaved Caspase 3. In addition, a model of choroidal neovascularization (CNV) was induced in both AnxA1 +/+ and
AnxA1 -/- mice. Vascular endothelial growth factor (VEGF-A, VEGF-C, VEGF-D), epidermal
growth factor (EGF), and endothelin-1 (ET-1) were evaluated using a multiplex assay.

Resultado

After 90 days, diabetic animals showed reduced body weight and increased blood
glucose levels compared to non-diabetic controls. AnxA +/+ DR mice showed radial Müller cell
gliosis demonstrated by strong GFAP immunoreactivity compared to the control and AnxA1 -/-
retinas. These histological findings were corroborated by increased levels of GFAP, vimentin
and cleaved caspase 3 in retinas from AnxA1 +/+ DR mice (*p <0.05 vs. control and AnxA1 -/- DR
mice). Despite no changes were detected for these markers between control and AnxA1 -/- DR
mice, high levels of glutamine synthetase were detected in AnxA1 -/- DR retinas compared to
AnxA1 +/+ DR ones (*p <0.05). Regarding growth and angiogenic factors, AnxA1 -/- DR retinas
show a significant increase in the levels of EGF, ET-1 and VEGF-C compared to their control.
They also showed elevated levels of VEGF-A compared to AnxA1 +/+ DR retinas. In the CNV
model, increased expression of ET-1 and VEGF-A was found in AnxA1 -/- CNV animals
compared to controls, while AnxA1 -/- CNV retinas exhibited higher expression of VEGF-C than
AnxA1 +/+ CNV ones.

Conclusão

The lack of AnxA1 produces changes in the levels of growth factors associated
with angiogenesis and endothelial dysfunction and contributes to greater protection of the retina
in the process of gliosis and degeneration induced by DR. Thus, AnxA1 represents a potential
target for the development of new therapeutic strategies for DR.