The aim of the present study is to evaluate the roles of TGFs β1 and β2, glial cell line-derived neurotrophic factor (GDNF), and nerve growth factor (NGF) in the pathogenesis of idiopathic epiretinal membrane (ERM).Eight patients, six males and two females, with an average age of 60.25 ± 17.16 years (range, 33-75 years) who were affected by idiopathic ERM were enrolled in the study. All patients underwent standard pars plana vitrectomy surgery with membrane removal and specific ELISA was performed to evaluate TGFβ1, TGFβ2, GDNF, and NGF in the vitreous samples. This was repeated after acidification of the samples with hydrochloric acid.Before acidification, ELISA analysis revealed a significant increase of TGFβ2 in the samples with idiopathic ERM (327.98 ± 99.58 pg/mL; range, 206.864-466.235 pg/mL) compared to the control group (187.17 ± 58.20 pg/mL; range, 132.758-271.707 pg/mL; t = 3.4; P < 0.05). A statistically significant difference was also obtained after acidification of the samples (618.15 ± 201.43 pg/mL; range, 409.795-866.215 pg/mL compared to 265.04 ± 98.15 pg/mL; range, 152.478-352.101 pg/mL; t = 4.5; P < 0.05). Notably, before acidification the differences in NGF between the two groups were not statistically significant (t = 0.79; P = 0.46), while after acidification a significant increase of the NGF levels in ERM samples was found in comparison with the control group (723.41 ± 235.4 vs. 242.84 ± 104.61; t = 3; P < 0.05).The present study reveals that TGFβ2 and NGF are associated with idiopathic ERMs, suggesting a novel compensatory mechanism so far never proposed.