Increased Glial Fibrillary Acid Protein and Vimentin in Vitreous Fluid as a Biomarker for Proliferative Vitreoretinopathy

Abstract

Purpose: Glial fibrillary acid protein (GFAP) and vimentin are type III intermediate filament proteins, ubiquitously expressed in retinal glial cells. Under retinal stress, both GFAP and vimentin are well-known sensitive markers 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 proliferative vitreoretinopathy (PVR).

Methods: Vitreous fluids were collected from 44 patients who underwent pars plana vitrectomy for macular hole (Group 1; n = 8), epiretinal membrane (Group 2; n = 8), or retinal detachment (RD) with various degrees of PVR (Group 3; n = 28). The severity of PVR was determined by cumulative scores using PVR classification. GFAP, vimentin, and total protein levels from the vitreous samples were measured.

Results: Both GFAP and vimentin levels were significantly elevated in vitreous fluid from Group 3 (RD) compared with Groups 1 and 2 (P < 0.01). GFAP levels (ng/mL) were 12.4 ± 9.8, 17.5 ± 17.7, and 572.0 ± 11659.7, and vimentin levels (ng/mL) were 40.8 ± 61.9, 88.6 ± 86.8, and 3952.8 ± 8179.5 in Groups 1, 2, and 3, respectively. Total protein levels were not significantly different among the three groups. Elevated GFAP and vimentin levels in Group 3 were positively correlated with the areas of RD (P < 0.01, r = 0.53 in GFAP and P < 0.05, r = 0.46 in vimentin) and PVR scores (P < 0.05, r = 0.46 in GFAP and P < 0.00001, r = 0.76 in vimentin).

Conclusions: Our data suggest that human vitreous GFAP and vimentin are protein biomarkers for PVR, and reactive gliosis may play a part in PVR formation.

Figure 1.

Vitreous GFAP, vimentin, and total protein levels in macular hole, epiretinal membrane, and retinal detachment. (A) Vitreous body GFAP level in retinal detachment, 572.0 ± 1159.7 ng/mL, was significantly higher than in macular hole, 12.4 ± 9.8 ng/mL (P < 0.01) and epiretinal membrane 17.5 ± 17.7 ng/mL (P < 0.01). (B) Vitreous body vimentin level in retinal detachment, 3952.8 ± 8179.5 ng/mL, was significantly higher than in macular hole, 40.8 ± 61.9 ng/mL (P < 0.01) and epiretinal membrane 88.6 ± 86.8 ng/mL (P < 0.01). (C) Vitreous body GFAP normalized to total protein level in retinal detachment, 202.1 ± 582.2 ng/mg total protein, was significantly higher than macular hole, 4.9 ± 3.3 ng/mg total protein (P < 0.01) and epiretinal membrane 3.3 ± 1.7 ng/mg total protein (P < 0.01). (D) Vitreous body vimentin normalized to total protein level in retinal detachment, 851.0 ± 1055.6 ng/mg total protein, was significantly higher than in macular hole, 16.3 ± 19.3 ng/mg total protein (P < 0.01) and epiretinal membrane 23.1 ± 21.0 ng/mg total protein (P < 0.01). (E) Vitreous body total protein level was not significantly different among macular hole, 3.1 ± 1.2 mg/mL, epiretinal membrane, 4.0 ± 2.0 mg/mL, and retinal detachment, 3.4 ± 2.6 mg/mL.

Figure 2.

Correlations between vitreous body GFAP, vimentin, and total proteins in retinal detachment and areas of retinal detachment and PVR scores. (A, B) Elevated vitreous body GFAP levels in retinal detachment were positively correlated with the areas of RD (P < 0.01, r = 0.53) and PVR scores (P < 0.05, r = 0.46). (C, D) Elevated vitreous body vimentin levels in retinal detachment were positively correlated with the areas of RD (P < 0.05, r = 0.46) and PVR scores (P < 0.00001, r = 0.76). (E, F) Vitreous body total protein was positively correlated with PVR scores (P < 0.00001, r = 0.74), but not with areas of retinal detachment.

Figure 3.

Correlations between vitreous body GFAP, vimentin, and total proteins in retinal detachment and duration of retinal detachment. (A, B) Elevated vitreous body GFAP and vimentin levels in retinal detachment were not correlated with the duration of retinal detachment. (C) Vitreous body total protein was not correlated with duration of retinal detachment.