The role of receptor MAS in microglia-driven retinal vascular development.

OBJECTIVE: The receptor MAS, encoded by Mas1, is expressed in microglia and its activation has been linked to anti-inflammatory actions. However, microglia are involved in several different processes in the central nervous system, including the promotion of angiogenesis. We therefore hypothesized that the receptor MAS also plays a role in angiogenesis via microglia. APPROACH AND RESULTS: To assess the role of MAS on vascular network development, flat-mounted retinas from 3-day-old wild-type (WT) and Mas1-/- mice were subjected to Isolectin B4 staining. The progression of the vascular front was reduced (- 24%, p < 0.0001) and vascular density decreased (- 38%, p < 0.001) in Mas1-/- compared to WT mice with no change in the junction density. The number of filopodia and filopodia bursts were decreased in Mas1-/- mice at the vascular front (- 21%, p < 0.05; - 29%, p < 0.0001, respectively). This was associated with a decreased number of vascular loops and decreased microglial density at the vascular front in Mas1-/- mice (-32%, p < 0.001; - 26%, p < 0.05, respectively). As the front of the developing vasculature is characterized by reduced oxygen levels, we determined the expression of Mas1 following hypoxia in primary microglia from 3-day-old WT mice. Hypoxia induced a 14-fold increase of Mas1 mRNA expression (p < 0.01). Moreover, stimulation of primary microglia with a MAS agonist induced expression of Notch1 (+ 57%, p < 0.05), Dll4 (+ 220%, p < 0.001) and Jag1 (+ 137%, p < 0.001), genes previously described to mediate microglia/endothelial cell interaction during angiogenesis. CONCLUSIONS: Our study demonstrates that the activation of MAS is important for microglia recruitment and vascular growth in the developing retina.

[Study of internal limiting membrane peeling in stage-3 and -4 idiopathic macular hole surgery]. / Etude de l'ablation de la limitante interne dans la chirurgie des trous maculaires idiopathiques de stade 3 et 4.

PURPOSE: To evaluate the advantages of peeling the internal limiting membrane (ILM) in macular hole surgery. PATIENTS AND METHODS: Retrospective analysis of the results of macular hole surgery, comparing two surgical protocols performed by the same surgeon. Both protocols included a standard pars plana vitrectomy with intravitreous nonexpansile gas and adjunction of autologous plasma over the macular hole. In addition, in the second group, the ILM of the eyes was systematically peeled after its coloring by indocyanine green (infracyanine) in the latter patients. RESULTS: We studied 39 eyes of 36 patients with stage-3 or -4 macular hole surgery. The duration of symptoms before surgery was on average 9 months. Twenty-one eyes (53.8%) underwent ILM peeling. Macular hole closure after one procedure was significantly more frequent postoperatively in the group of eyes with ILM peeling than in the other group (90% and 50%, respectively, p<0.01); after two procedures, macular hole closure reached 61% in the second group. The macular hole seemed to have disappeared on angiographic examination and on OCT in 90% of eyes with anatomical success in the group with ILM peeling and in only 22% of eyes with anatomical success in the group without. Visual acuity improved by two lines or more in 62% of eyes with ILM peeling and in 44% of eyes without. The difference in improvement in the macular threshold was statistically significant (p<0.001). CONCLUSION: This study would suggest that peeling of the ILM is an important adjuvant for successful closure of macular holes. Its possible mechanism of action is discussed. Further studies are needed to confirm these data by controlled randomized trial.