Increased Glial Fibrillary Acid Protein (GFAP) and Vimentin in Vitreous Fluid as a Biomarker for Proliferative Vitreoretinopathy (PVR).

Abstract

Purpose : GFAP and vimentin are the most abundant type III intermediate filament proteins of the retina, ubiquitously expressed in retinal glial cells. Under retinal stress, both GFAP and vimentin are dramatically up-regulated and serve as a well-known sensitive marker for retinal gliosis. However, little is known about whether these proteins are released into the vitreous body in response to retinal gliosis or are related to the severity of retinal gliosis seen in PVR. We hypothesized that increased GFAP and vimentin from retinal gliosis are released into the vitreous body, and are correlated with the severity of PVR.

Methods : Undiluted vitreous fluids were collected from 46 patients who underwent pars plana vitrectomy for macular hole (Group 1; N=8), epiretinal membrane (Group 2; N=8), or retinal detachment with various degrees of proliferative vitreoretinopathy (PVR) (Group 3; N=30). The severity of retinal gliosis was determined by areas of retinal detachment, duration of symptoms, and cumulative scores using PVR classification. GFAP and vimentin levels from the vitreous samples were measured using ELISA and BCA reagent was used for total protein determination. Data were expressed as mean ± SD. Mann-Whitney U test and Spearman correlation coefficient were used for statistical analyses (p<0.05).

Results : Both GFAP and vimentin levels were significantly elevated in vitreous fluid from retinal detachment (Group 3) compared with macular hole (Group 1) or epiretinal membrane (Group 2) (p<0.05). GFAP levels (ng/mL) were 12.3±9.8, 14.0±13.1, and 533.8±1128.3 in Group 1,2, and 3 respectively. Vimentin levels (ng/mL) were 40.7±61.8, 84.5± 92.9, and 3582.2±7980.1 in Group 1,2, and 3, respectively. Total protein levels were not significantly different between the three groups. Elevated GFAP and vimentin levels in Group 3 were positively correlated with the areas of retinal detachment (p=0.007, R²=0.251 in GFAP and p=0.026, R²=0.179 in vimentin) and PVR scores (p=0.014, R2=0.219 in GFAP and p=0.016, R²=0.208 in vimentin), but not with the duration of retinal detachment (Figure). Total protein was not correlated with any of these parameters.

Conclusions : Our data suggest that human vitreous GFAP and vimentin are protein biomarkers for PVR and glial activation is a key step in PVR formation. Further study is needed to examine the functional role of GFAP and vimentin in PVR.

This is a 2020 ARVO Annual Meeting abstract.