Page 89 - 83_01

Targeting inflammation in the retina: a new therapeutic approach in diabetic retinopathy

Based on these analysis of the inflammatory profile of their respective untreated retinas (Figure 7A). Moreover,
the retina in db/db mice during DR progression, we reactive gliosis, which was already present in retinas from
performed the ex vivo analysis in retinal explants at 8 db/db mice at 8 weeks (28) was maintained in retinal
weeks of age. Retinal explants from 8 weeks old db/+ and explants and decreased by the treatment with R-DS-ONJ
db/db mice treated for 24 h with R-DS-ONJ showed (Figure 7B).
increased arginase-1 expression (M2 marker) compared to

Figure 7. Retinal gliosis is detected in 8 weeks-old db/db mice. Retinal explants from 8 weeks old db/+ and db/db mice were treated for

24 h with R-DS-ONJ. A) Western blot for arginase-1 (n=5 retinas per condition) G) Representative immunostaining for GFAP in whole

retina.

4. DISCUSSION therefore, these mice have been extensively used to study
relevant processes such as retinal vascular leakage and
T2D is considered a chronic low-grade systemic neurodegeneration, as well to test potential
inflammatory disease characterized by changes in both the pharmacological approaches (20, 35). Herein we have used
secretion of cytokines and the polarization of tissue- for the first time db/db mice to characterize the microglia
resident macrophages towards a M1 state (29-31) as polarization during DR in a systemic pro-inflammatory
demonstrated by the increased plasma levels of pro- environment. Notably, at 5 weeks of age, systemic
inflammatory cytokines and C-reactive protein found in endotoxemia was detected in db/db mice, probably
diabetic patients (32, 33). Among diabetic complications, reflecting alterations in intestinal barrier permeability and
DR is a multifactorial disease in which hyperglycaemia, gut microbiota at this early period (36, 37). Although
inflammation and neuronal dysfunction are major factors circulating TNFa and IL6 are elevated in 5 weeks old
involved in its etiopathology (34). db/db mice (results not shown), the local inflammation in

db/db mice recapitulate human DR progression and, the retina was not manifested at this age since mRNA

@Real Academia Nacional de Farmacia. Spain 89