Effect of intravitreal ranibizumab on fibrovascular membranes in patients with proliferative diabetic retinopathy

? AIM: To assess the effects of intravitreal ranibizumab (IVR) on angiogenesis and glial activity of the fibrovascular membrane (FVM) in patients with proliferative diabetic retinopathy (PDR).? METHODS: Forty-two eyes from 42 patients with PDR requiring vitrectomy were included and divided into two groups: control group (n=16) did not receive IVR, while IVR group (n=26) underwent IVR 5d before vitrectomy. FVM specimens were collected by the same surgeon during the interventions. Histopathological morphology was examined by hematoxylin-eosin (H-E) staining and cell densities in the FVM was assessed. Microvessels were outlined by immunohistochemical staining of CD31 and microvessel density (MVD) assessed as an index of FVM angiogenesis. Dual-color immunofluorescence staining, and confocal microscopy was used to detect co-localization and relative expression levels of glial fibrillary acidic protein (GFAP) and alpha-smooth muscle actin (alpha-SMA) as markers of glial-mesenchymal transition (GMT). The GMT index (GI; ratio of relative GFAP/alpha-SMA expression) was used to semi-quantify the degree of GMT or glial activity of FVMs.? RESULTS: H-E staining showed similar vascularization in both groups, with microvessels and scattered stromal cells in the matrix. Infiltrated cell densities did not differ significantly between the two groups (P>0.05). The MVD of the IVR group (130.62 +/- 15.46/mm2) was significantly lower than that of the controls (142.25 +/- 19.16/mm2, P<0.05). In both groups, all sections were strongly immunostained for GFAP and alpha-SMA. The Pearson's correlation coefficients (PCC) of intensity of automated pixel count of two markers indicated GFAP and alpha-SMA co-stained well and GMT participated in the remolding of FVMs in PDR. The mean relative GFAP expression in the IVR group was significantly lower, whereas that of alpha-SMA was significantly higher than in controls (P<0.05). GI in the IVR group (1.10 +/- 0.10) was significantly lower than in the controls (1.21 +/- 0.12, P<0.05).? CONCLUSION: IVR can reduce angiogenesis, glial activity of FVM and promote glial-fibrotic transformation by reducing MVD and promoting GMT but does not decrease the cell density in patients with PDR.

Automated summary

This study assessed the effects of intravitreal ranibizumab (IVR) on angiogenesis and glial activity of the fibrovascular membrane (FVM) in patients with proliferative diabetic retinopathy (PDR). The results showed that IVR can reduce angiogenesis and glial activity of FVM, promote glial-fibrotic transformation, but does not decrease cell density.